Complete androgen insensitivity due to deletion of exon C of the androgen receptor gene highlights the functional importance of the second zinc finger of the androgen receptor in vivo. Androgen-dependent gene transcription is mediated by the androgen receptor (AR) through interaction of its central zinc finger region with specific DNA sequences on target genes. Failure of this receptor-mediated gene transcription results in end organ resistance to androgens-the androgen insensitivity syndromes. In a pair of siblings with complete androgen insensitivity who had supranormal levels of androgen binding in genital skin fibroblasts, polymerase chain reaction and Southern blot analysis of the androgen receptor gene confirmed by polymerase chain reaction and sequence analysis of AR cDNA, revealed an in-frame deletion of exon C encoding the second zinc finger of the receptor. The mutant receptor in cultured genital skin fibroblasts had normal androgen binding affinity and was localized in the nucleus but had markedly reduced DNA-binding affinity. When recreated in vitro and tested in a cotransfection assay system the mutant receptor failed to activate transcription of an androgen-responsive reporter gene. This naturally occurring mutation highlights the functional dependence of the AR upon its second zinc finger in vivo and explains the complete insensitivity to androgen manifest by the affected individuals despite increased androgen binding. The elevated AR levels in the subjects' genital skin fibroblasts further suggests a possible role for the second zinc finger in autoregulation of receptor levels in vivo.


Genetic analysis of the human type-1 angiotensin II receptor. Angiotensin II is a potent pressor hormone and a primary regulator of aldosterone secretion. It acts through at least two types of receptors termed AT1 and AT2. We analyzed cDNA and genomic clones encoding the human angiotensin II type-1 receptor, AT1. The human AT1 gene was mapped to chromosome 3q by polymerase chain reaction analysis of DNA from a panel of human-hamster somatic cell hybrids. The predicted amino acid sequence is 95% identical to the corresponding rat and bovine receptors and 25% and 22% identical, respectively, to the receptors encoded by the RTA and MAS genes. Characterization of several human cDNA clones demonstrated the existence of two alternate 5'-untranslated regions (UTRs) that contain a common initial sequence but differ by the presence or absence of an insertion of 84 base pairs. In the genomic sequence, the coding sequences are contained in a single exon, with an intron occurring in the 5'-UTR at the position of insertion of the 84-base pair sequence. The exons encoding the alternate 5'-UTRs are located at least 3.8 kilobases away from the exon encoding the protein. Reverse transcription-polymerase chain reaction analysis showed that both forms of 5'-UTR are present in approximately equal abundance in a range of tissues expressing AT1. The reagents developed in this work may be useful in testing the hypothesis that genetic variations in angiotensin II receptor function are associated with a tendency to develop hypertension.


The role of asparagine-linked oligosaccharides in the subunit structure, steroid binding, and secretion of androgen-binding protein. Testicular androgen-binding protein (ABP) and liver sex hormone-binding globulin are encoded by the same gene. These proteins have the same primary amino acid sequences, but they differ in attached oligosaccharides; the differences are presumably due to cell-specific glycosylation mechanisms. To investigate the role of oligosaccharides in ABP/sex hormone-binding globulin subunit structure, secretion, and steroid binding, mutant rat ABP proteins were constructed that eliminated one or both of the two potential sites of asparagine (Asn)-linked glycosylation. Immunoblot analysis of wild type recombinant ABP yielded the typical heterogeneous banding pattern. Secreted ABP was composed of two protomers of M(r) 46,000 and M(r) 43,000, while cellular ABP yielded three mol wt species (M(r) 43,000, 41,000, and 39,000). Substitution of the Asn residue in either consensus sequence for Asn-linked glycosylation with an Ile residue resulted in increased mobility of the immunoreactive ABP species. These changes are consistent with the loss of an Asn-linked oligosaccharide. Substitution of both Asn residues yielded a single immunoreactive species in the medium and cell extracts that migrated as a M(r) 39,000 protein. These results demonstrate that the mol wt heterogeneity of ABP is due to differential Asn-linked glycosylation of both potential sites. All three mutant forms of ABP were secreted by the COS cells. However, the amount of immunoreactive ABP and [3H]5 alpha-dihydrotestosterone binding in the medium was lower than wild type (100%) in one of the single mutants (65%) and in the double mutant (29%). Unlike the glycosylation mutants, alteration of other residues, not involved in glycosylation, yielded cellular ABP and no detectable medium ABP.(ABSTRACT TRUNCATED AT 250 WORDS)


CCAAT/enhancer binding protein expression is rapidly extinguished in TA1 adipocyte cells treated with tumor necrosis factor. Tumor necrosis factor (TNF) has been shown to have diverse effects on a wide variety of cell types. In the mouse adipogenic TA1 cell line, TNF completely abolishes differentiation and reverts fully differentiated fat cells into fibroblasts. This block in differentiation and its reversal is due to the rapid reduction in the expression of adipose-specific genes. This study reports that the transcription factor, CCAAT/enhancer binding protein (C/EBP), previously reported to promote the differentiation of 3T3-L1 adipocytes, is expressed in TA1 cells. During their growth in culture, the levels of C/EBP, as evidenced by its cellular levels of specific mRNA, protein, and DNA binding activity, increase dramatically when cells reach confluence and proceed to differentiate. Addition of TNF to cultured preadipocytes or fully differentiated adipocytes rapidly reduces C/EBP levels and is accompanied by the decrease in expression of adipose-specific genes. C/EBP binding sites occur in several adipose-specific genes, and here it is demonstrated that its presence in a novel adipose-specific gene, Clone 47, also referred to as FSP27, may be responsible for the strong down-regulation of the expression of the Clone 47 (FSP27) promoter-linked chloramphenicol acetyl transferase gene by TNF. This study proposes that the loss of C/EBP in response to TNF treatment may in part explain the loss of the adipocyte differentiated state.


Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors. T3 binds to intranuclear thyroid hormone receptors (TRs) on target DNA elements and exerts profound influences on gene expression by mechanisms not yet characterized. We used gel shift assays and cross-linking experiments to demonstrate that T3 greatly induced the monomeric binding of the hTR beta produced in Escherichia coli to DNA. T3 also increased the gel mobility of these monomer-DNA complexes suggesting they undergo a ligand-induced conformational change. This effect did not depend on the orientation and spacing of the half-site motifs within the DNA structure. In contrast, T3 had diverse effects on the dimeric interaction. T3 increased the dimeric interaction to the palindrome GGTCA.TGACC (an effect lost by spacing the half-sites with 3 base pairs) and decreased the dimeric interaction to the inverted palindrome containing the TGACC.GGTCA motif. Scatchard analyses indicated that the T3 enhancement on binding was due to an increase in the number of TR with high affinity DNA-binding activity and not by increasing the affinity of TR that could bind to DNA. The effects of various T3 analogs were directly related to their affinities for the TR. These ligand effects on in vitro TR-DNA binding may reflect mechanisms by which T3 regulates transcription in vivo.


Leakage of carbonic anhydrase III from normal and denervated rat skeletal muscle following contractile activity. Skeletal muscle extracellular carbonic anhydrase III was investigated in anesthetized rats by a microdialysis technique. A small dialysis probe was inserted into the tibialis anterior (TA) muscle and perfused continuously. Perfusates were collected before and during muscle contraction, induced by electrical stimulation of the muscle or of the sciatic nerve. In the perfusate of resting normal and denervated muscle, the concentration of CA III was 10 to 12 ng/mL, as measured by a radioimmunosorbent technique. During contractile activity, the concentrations of CA III increased markedly in the normal and denervated muscle. A TA muscle suspended in physiological saline behaved similarly, even though the leakage before and during contraction was higher than in vivo. The results show that skeletal muscle leaks CA III both in vivo and in vitro, a leakage which was markedly increased by contractile activity. The microdialysis technique should also be useful in humans to study the efflux of various proteins from different kinds of diseased or fatigued muscles.


Single motor unit H-reflex in motor neuron disorders. The latency fluctuation of single motor unit potentials (MUPH) in the H-reflex is greater than the latency fluctuation of MUPs in the direct (MUPM) and recurrent (MUPF) responses. This has been attributed to the variability in the impulse generation at the site of nerve stimulation, and to the variation in the synaptic delay at the anterior horn cell. We studied the latency fluctuation of single motor unit H-reflex in patients with motor neuron disorders (MND) in comparison with normal subjects. The mean jitter of the H-reflex was 264.3 +/- 17.8 microseconds (mean +/- SEM) in 30 MUPH recorded from 10 patients with ALS, 302.7 +/- 25.2 microseconds in 16 MUPH from 6 patients with chronic motor neuron diseases, as compared with 137.4 +/- 7.3 microseconds in 34 MUPH recorded from 10 normal subjects. This difference, which persisted even after the correction for the latency variation of MUPM, cannot be explained on the basis of an enhanced reciprocal inhibition. Thus, the increased latency fluctuation of the single motor unit H-reflex in patients with MND may reflect changes in the motoneuron pool excitability that may be secondary to altered intrinsic electrophysiological properties of motoneurons, or to an abnormal temporal and spatial summation of synaptic inputs on motoneurons.


Beneficial effects of training on developing dystrophic muscle. The objective of this study was to determine whether increased contractile activity is beneficial or detrimental to developing dystrophic muscle. Hamsters (20-days-old) were gradually introduced to running at a speed of 14 m/min at 10% grade for 2 (T2) or 4 (T4) h/d for 4 weeks, 5 d/wk. Histological and fiber type properties were determined in the soleus (SOL), plantaris (PL), and extensor digitorum longus and contractile properties in SOL and PL from 5 animals/group, including 5 controls. Experimental animals had normal body and muscle mass. Training for 2 h/d had little effect on SOL contractile properties, whereas 4 h/d resulted in significant increases in force, percentage of type I fibers, and type I hypertrophy. Force also increased in PL. Muscle necrosis was reduced in SOL (T2 and T4) and unchanged in PL. In conclusion, endurance training generally had a beneficial or, at least, no detrimental effect on developing dystrophic muscles.


Needle electromyography of the diaphragm. A method is described for performing needle electromyography of the diaphragm which is safe and causes little discomfort. It provides valuable information concerning neuropathies and myopathies which may affect the diaphragm, and complements information derived from phrenic nerve conduction studies. Firing patterns of motor unit potentials during spontaneous respiration identify upper motor neurone disorders causing respiratory insufficiency.


Neuromuscular causes of prolonged ventilator dependency. We prospectively evaluated 21 patients with prolonged ventilator dependency, to determine the frequency of unsuspected neuromuscular disease as a cause of this condition, and to determine the types of such diseases. Assessment was performed with routine and specialized electrophysiologic procedures. None of the patients had known prior neuromuscular disease, and none had ongoing medical problems that could account for their continued ventilator dependency. Sixty-two percent were found to have a neuromuscular disease severe enough to account for the ventilator dependency. Most of the remaining cases had a contributory neuromuscular disease. In addition to critical illness polyneuropathy, several other significant categories were identified. Myopathic EMG changes were found in 50% of the subgroup assessed by quantitative EMG. We conclude that neuromuscular disease is the most important factor in prolonged ventilator dependency, and that diseases other than critical illness polyneuropathy represent an important cause of this syndrome.


Reciprocal changes in myosin isoform mRNAs of rabbit skeletal muscle in response to the initiation and cessation of chronic electrical stimulation. Changes in myosin heavy chain (MHC) mRNAs were studied in rabbit fast-twitch muscles during continuous electrical stimulation at 10 Hz for periods up to 3 weeks, and during the first 12 days of the recovery process that followed cessation of 6 weeks' stimulation. Two cDNA probes were used to detect MHC mRNAs specific to fast- and slow-twitch skeletal muscle in RNase protection assays and Northern- and slot-blot analyses. The isolation and base sequence of one of these probes, corresponding to the MHC gene expressed in soleus (slow-twitch), is described. At an early stage of the response to stimulation, fast MHC mRNA was replaced by slow MHC mRNA. During recovery, this process occurred in reverse but took longer. The time course of recovery was slightly faster in tibialis anterior than in extensor digitorum longus. The changes in mRNAs during both stimulation and recovery reflected changes in the corresponding muscle proteins.


Localization of nerve depolarization with magnetic stimulation. The specific location on the magnetic stimulation (MS) coil that may correspond to the area of nerve depolarization has not been determined. In order to localize such an area, MS with 9-cm and 5-cm diameter coils was compared with conventional percutaneous electric stimulation (ES). On the 9-cm coil the distribution of points of nerve depolarization corresponded to that quarter of the coil which was placed over and parallel to the median nerve, whereas on the 5-cm coil, this area also extended outside the coil. The points of median nerve depolarization with MS were distributed over a distance of 7 cm on the stimulator head and was nearly identical for the 2 coil sizes at the wrist and elbow. Ulnar nerve costimulation was less frequent with the smaller coil at the wrist. A calculated reference point on the coil is suggested for more accurate NCV determinations.


Changes in mast-cell distribution in skeletal muscle after denervation. Motor nerves are known to govern the structure of skeletal muscle. In the normal guinea pig diaphragmatic muscle, we found that mast cells were predominantly located in the central tendon. Following denervation, these cells became more numerous in the muscle itself than in the tendon. Therefore, nervous trophic influences are exerted on other tissue elements besides those which sustain transmission and contraction. Ascertaining mast-cell distribution in biopsies may help to elucidate denervation effects in motor neuron disease.


Cutaneous reflexes in Parkinson's disease. The physiology of rigidity in Parkinson's disease (PD) can be investigated by the study of reflexes. Cutaneous reflexes (CR) were measured in 10 patients with PD and in 10 age- and sex-matched normal volunteers. EMG activity was recorded from the first dorsal interosseous muscle with surface electrodes, rectified and averaged. The index finger was stimulated with an intensity four times the sensory threshold. The subjects abducted the index finger with 20% of maximal force. While the latencies of the different reflex components and the amplitudes of the excitatory peaks were not different in the two groups, the first inhibitory component was less pronounced in patients with PD as compared with normals. This effect is partially reversed with dopaminergic drug treatment. The results are compatible with the loss of an inhibitory spinal mechanism elicited by cutaneous afferents, and can be a partial explanation for increased tone in PD.


Dominantly inherited malignant hyperthermia (MH) in the King-Denborough syndrome. A 14-year-old boy, an only child, with the phenotypical dysmorphic features of the King-Denborough Syndrome developed a severe hyperthermic episode during anesthesia which responded to the administration of sodium dantrolene. As adequate metabolic studies were not available at the time of the crisis he was referred for confirmation of the malignant hyperthermia (MH) status. Muscle tension studies confirmed the presence of MH. The patient's mother and father were subsequently tested and the mother was found to be MH positive, the father MH negative.


Genetic influence on smoking--a study of male twins. The results of twin and family studies suggest that heredity has a small influence on smoking behavior. We conducted a genetic analysis of several aspects of smoking behavior among subjects in the National Academy of Sciences-National Research Council Twin Registry. The registry includes male twins who were born in the United States between 1917 and 1927 and who were members of the armed services during World War II. Information on smoking history was available for 4775 pairs of twins, who were first surveyed in 1967 through 1969, when they were 40 to 50 years old, and then re-surveyed in 1983 through 1985, when they were 56 to 66. Eighty percent of the subjects in this cohort had smoked at some time in their lives, 60 percent were smokers in 1967 through 1969, and 39 percent were smoking in 1983 through 1985. Similarities between twins in smoking habits at base line and at the second follow-up 16 years later were examined. The comparison of concordance for smoking between monozygotic and dizygotic twins was used to assess the relative contribution of familial and genetic factors. In 1967-1969 survey the ratio of observed to expected concordance for smoking was higher among the monozygotic twins than among the dizygotic twins for those who had never smoked (overall rate ratio, 1.38; 95 percent confidence interval, 1.25 to 1.54), for former smokers (overall rate ratio, 1.59; 95 percent confidence interval, 1.35 to 1.85), for current cigarette smokers (overall rate ratio, 1.18; 95 percent confidence interval, 1.11 to 1.26), and for current cigar or pipe smokers (overall rate ratio, 1.60; 95 percent confidence interval, 1.22 to 2.06). The data also suggest genetic influences on quitting smoking. Monozygotic twins were more likely than dizygotic twins to be concordant for quitting smoking (overall rate ratio, 1.24; 95 percent confidence interval, 1.06 to 1.45). In this cohort of adult male twins, there were moderate genetic influences on lifetime smoking practices.


Survival of nationally shared, HLA-matched kidney transplants from cadaveric donors. The UNOS Scientific Renal Transplant Registry. The importance of HLA histocompatibility typing to the outcome of transplantation of cadaveric kidneys has been controversial. Four years ago, a prospective trial began in all U.S. transplantation centers to determine whether the results of transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to waiting patients undergoing dialysis when there was a match at the HLA-A, B, and DR loci. A total of 1386 cadaveric kidneys were shipped from 108 organ centers to 198 transplantation centers and distributed among HLA-matched recipients, 1004 of whom were receiving a first transplant and 382 of whom were receiving a subsequent transplant. Graft survival in these recipients was compared with that in 22,188 recipients of first transplants and 3950 recipients of subsequent transplants whose HLA antigens differed from those of the donor. The rate of graft survival at one year in recipients of HLA-matched first transplants was 88 percent, as compared with 79 percent in the recipients of mismatched grafts (P less than 0.001). The estimated half-life of the kidney after the first year was 17.3 years for matched grafts, as compared with 7.8 years for mismatched grafts (P = 0.003). Among paired kidneys from 470 donors, one-year graft survival was 87 percent in the recipients of matched first grafts, as compared with 80 percent in the recipients of the contralateral kidneys, who did not have HLA matches with the donors. In donors and recipients matched for the more highly defined split Class I and Class II HLA antigens, the rate of graft survival after one year was as high as 90 percent. The collaborative renal-transplantation program for HLA matching of donors and recipients yielded an increased rate of one-year graft survival and an estimated half-life for matched grafts twice that for mismatched grafts. An increased role for HLA matching in kidney allocation is therefore indicated.


Racial differences in the survival of cadaveric renal allografts. Overriding effects of HLA matching and socioeconomic factors. The long-term survival of cadaveric renal allografts is lower in black recipients than in white recipients, although the one-year graft survival is similar in these racial groups. We sought to determine what factors account for this disparity. We studied 100 consecutive recipients of primary cadaveric renal allografts (57 were black and 43 white) at least 1 year after transplantation (mean, 40 months); all had received identical immunosuppressive therapy. We evaluated differences in the cause and duration of end-stage renal disease, the number of pretransplantation transfusions, age, matching for HLA-A, B, and DR antigens, race of the donor, insurance coverage, and compliance to assess their effect on graft survival in both groups. Allograft survival after one year was significantly lower in black than in white patients (P = 0.025). According to univariate analysis, only the recipient's age at transplantation, the number of mismatches for HLA antigens, the type of insurance coverage, the source of referral for transplantation, and the degree of compliance correlated significantly with the rate of graft survival. The frequency of all variables that reduced graft survival was higher among the blacks. According to proportional-hazards analysis, the only factors contributing to a lower rate of graft survival were age of less than 30 years at transplantation (relative risk, 2.3; 95 percent confidence interval, 1.3 to 4.6), mismatches for all six HLA antigens as compared with three or fewer mismatches (relative risk, 5.6; 95 percent confidence interval, 3.3 to 9.6), and coverage by Medicaid or Medicare (relative risk, 2.2; 95 percent confidence interval, 1.5 to 3.2). Race had no additional effect. Noncompliance was more frequent among blacks (16 percent vs. 2 percent) and could substitute for insurance status in the model. When immunosuppression is equivalent in black and white transplant recipients, apparently race-related differences in the long-term survival of renal cadaveric allografts appear to be related to other factors that affect graft survival unfavorably, notably poor HLA matching and unfavorable socioeconomic factors.


The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. The familial long-QT syndrome is characterized by a prolonged QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. It is not certain, however, that the length of the QT interval is a sensitive or a specific diagnostic criterion. Recently, we identified genetic markers on chromosome 11 that distinguished between carriers and noncarriers of the gene for the long-QT syndrome in three families. In this study, we compared the clinical features of carriers and noncarriers and assessed the diagnostic accuracy of the QT interval. We obtained medical histories and electrocardiograms from 199 family members. QT intervals corrected for heart rate (QTc) were determined independently by two blinded investigators. Carriers of the long-QT gene (83 subjects) and noncarriers (116 subjects) were distinguished by genetic-linkage analysis. Fifty-two of the carriers of the long-QT gene (63 percent) had a history of syncope, whereas four (5 percent) had a history of aborted sudden death. The QTc intervals of the gene carriers ranged from 0.41 to 0.59 second (mean, 0.49). By contrast, the QTc intervals of the noncarriers ranged from 0.38 to 0.47 second (mean, 0.42). On average, carriers of the gene for the long-QT syndrome had longer QTc intervals than noncarriers, but there was substantial overlap (in 126 of the 199 subjects, or 63 percent). The use of a QTc interval above 0.44 second as a diagnostic criterion resulted in 22 misclassifications among the 199 family members (11 percent). QTc intervals of 0.47 second or longer in males and 0.48 second or longer in females were completely predictive but resulted in false negative diagnoses in 40 percent of the males and 20 percent of the females. In families affected by the long-QT syndrome, measurement of the QTc interval may not permit an accurate diagnosis. DNA markers make it possible to make a genetic diagnosis in some families, but not all gene carriers have symptoms.


Risk factors for fatal residential fires. Residential fires are the most important cause of fire-related mortality in the United States. Previous research has concentrated on fatal fires in urban areas; considerably less is known about fatal fires in rural areas. We studied fatal and nonfatal residential fires in predominantly rural areas. Using a case-control design, we compared all 151 fatal fires (cases) in single-family dwellings in North Carolina during a 13-month period with a sample of nonfatal fires (controls). Case fires were identified through the medical-examiner system, and control fires that occurred within a few weeks of the case fires were chosen from the records of randomly selected fire departments statewide. For each fire, fire officials were interviewed about the dwelling, the fire, the people involved, and the fire-response system. Although heating incidents were the leading cause of fires, fatal fires were more likely to have been caused by smoking (31 percent of fatal fires vs. 6 percent of nonfatal fires). Mobile homes posed a higher risk of death if a fire occurred (odds ratio, 1.7; 95 percent confidence interval, 1.1 to 2.6), as did the absence of a smoke detector (odds ratio, 3.4; 95 percent confidence interval, 2.1 to 5.6). Smoke detectors were more protective against death in fires involving young children and when no one present was impaired by alcohol or drugs or had a physical or mental disability. The presence of an alcohol-impaired person was the strongest independent risk factor for death in the case of a fire (odds ratio, 7.5; 95 percent confidence interval, 4.4 to 12.7). Residential fires are most likely to be caused by heating equipment or smoking materials. The risk of death is greatest in fires in mobile homes, in those involving alcohol-impaired persons, and in those in houses without smoke detectors.


Addition and subtraction by human infants. Human infants can discriminate between different small numbers of items, and can determine numerical equivalence across perceptual modalities. This may indicate the possession of true numerical concepts. Alternatively, purely perceptual discriminations may underlie these abilities. This debate addresses the nature of subitization, the ability to quantify small numbers of items without conscious counting. Subitization may involve the holistic recognition of canonical perceptual patterns that do not reveal ordinal relationships between the numbers, or may instead be an iterative or 'counting' process that specifies these numerical relationships. Here I show that 5-month-old infants can calculate the results of simple arithmetical operations on small numbers of items. This indicates that infants possess true numerical concepts, and suggests that humans are innately endowed with arithmetical abilities. It also suggests that subitization is a process that encodes ordinal information, not a pattern-recognition process yielding non-numerical percepts.


A test of reciprocal X-Y interactions as a cause of hybrid sterility in Drosophila. Elucidation of the nature of the gene interactions that underly the sterility of interspecific hybrids is important in evolutionary biology. The interactions between the heterospecific X and Y (or Z and W) chromosomes are often used as an explanation for two reasons. First, the fertility of the hybrids of the heterogametic sex is much more often affected than that of the homogametic sex (Haldane's rule) and X-Y interactions are specific to the heterogametic sex. Second, sex chromosomes, especially the X chromosome, are often considered to be of special importance in determining the fertility of hybrids. X-Y interactions have been addressed in studies of males with a heterospecific Y chromosome in a mixed genetic background. A more stringent test of the X-Y interaction model requires each X chromosome sterility factor to be tested separately for its interaction with the Y chromosome in a homogeneous background of the pure species. Here we report such a test of the X-Y interaction model and conclude that X-Y interactions should not be assumed to be the only or even the most common cause of hybrid sterility.


Mixed parvocellular and magnocellular geniculate signals in visual area V4. Visual information from the retina is transmitted to the cerebral cortex by way of the lateral geniculate nucleus (LGN) in the thalamus. In primates, most of the retinal ganglion cells that project to the LGN belong to one of two classes, P and M, whose axons terminate in the parvocellular or magnocellular subdivisions of the LGN. These cell classes give rise to two channels that have been distinguished anatomically, physiologically and behaviourally. The visual cortex also can be subdivided into two pathways, one specialized for motion processing and the other for colour and form information. Several lines of indirect evidence have suggested a close correspondence between the subcortical and cortical pathways, such that the M channel provides input to the motion pathway and the P channel drives the colour/form pathway. This hypothesis was tested directly by selectively inactivating either the magnocellular or parvocellular subdivision of the LGN and recording the effects on visual responses in the cortex. We have previously reported that, in accordance with the hypothesis, responses in the motion pathway in the cortex depend primarily on magnocellular LGN. We now report that in the colour/form pathway, visual responses depend on both P and M input. These results argue against a simple correspondence between the subcortical and cortical pathways.


The structure of ribosomal protein S5 reveals sites of interaction with 16S rRNA. Understanding the process whereby the ribosome translates the genetic code into protein molecules will ultimately require high-resolution structural information, and we report here the first crystal structure of a protein from the small ribosomal subunit. This protein, S5, has a molecular mass of 17,500 and is highly conserved in all lifeforms. The molecule contains two distinct alpha/beta domains that have structural similarities to several other proteins that are components of ribonucleoprotein complexes. Mutations in S5 result in several phenotypes which suggest that S5 may have a role in translational fidelity and translocation. These include ribosome ambiguity or ram, reversion from streptomycin dependence and resistance to spectinomycin. Also, a cold-sensitive, spectinomycin-resistant mutant of S5 has been identified which is defective in initiation. Here we show that these mutations map to two distinct regions of the molecule which seem to be sites of interaction with ribosomal RNA. A structure/function analysis of the molecule reveals discrepancies with current models of the 30S subunit.


An interview with Angela Skalla and Luke McGuinness. Interview by Connie R. Curran. The partnership between the chief executive officer and chief nurse officer is vital for driving quality improvement and delivering outstanding patient care while containing or reducing costs. These two leaders must create and communicate a vision statement to lead and build a strong management team.


Unit-based clinical nurse specialist: redesigning nursing services. At the Johns Hopkins Hospital, the Medical Nursing Services redesigned its delivery of direct patient care to include nurse managers, staff nurses, nursing support technicians, and unit-based clinical nurse specialists (CNSs). The CNS role proved efficacious to both nursing staff and nurse managers.


Nursing challenges in managed care.

Nursing challenges in managed care. The emergence of managed care organizations offers many opportunities, challenges, and threats for nursing and nurses. The goal of these organizations (ensuring maximum value from resources used) is congruent with the basic philosophy of nursing, which focuses on the total needs of the patient, not just disease, and on maintaining the health of the individual to minimize the need for expensive health care services. Within the structure of managed care, however, there is also a need for strong professional advocacy to ensure that the needs of the members are adequately met as the organization strives to maintain costs. In meeting the needs of the organization and of the members, the nurse also plays an important role in managing the resources used in producing health care services.


Restructuring nursing care delivery systems. Job design and system redesign theory are applied to elucidate costs and benefits of alternative restructuring schemes. Strategies are outlined for nurse executives to use for successful reconceptualization of nursing positions.


Nursing care costs for a DRG sub-group.

Nursing care costs for a DRG sub-group. This study determined the average cost of nursing care for two DRGs and evaluated how a specific nursing intervention, Phase I Cardiac Rehabilitation, impacts on these costs. A unit-based methodology to determine the cost of providing nursing care to patients who stay on more than one nursing care unit during their hospital stay will facilitate decision making by nurse administrators and clinicians to contain rising health care costs.


Use of electroneuronography in monitoring facial nerve paralysis. FNP is a disease entity seen in a variety of clinical settings. We recommend early ENoG evaluation of every total facial nerve paralysis to assess the percentage of degeneration. ENoG is an objective, permanent record with prognostic significance especially in 16% of those patients who are predicted to have a poor outcome without further intervention. In consultation with the patient a treatment plan can thus be proposed to optimize the opportunity for recovery.


Sex steroid hormones in the pathogenesis of chronic subdural haematoma. In order to verify whether hormonal factors could be involved in the pathogenesis of Chronic Subdural Haematoma (CSDH), based on clinical and epidemiological demonstration of higher incidence of this disease in male patients and particularly in those with high urinary estrogen values, Estradiol (ER) and Progesterone (PR) Receptors were studied in the Haematoma External Membrane (HEM) in 18 male and 7 female CSDH patients. The observed higher incidence of ER and PR in male rather than in female patients (73% vs 27% and 72% vs 28% for male and female patients respectively), and the higher concentration of ER in the HEM of male rather then female patients (55 +/- 15 S.E. vs 13 +/- 7 S.E. fmol/mg protein) suggest that this pathological process, which affects individuals whose gonadal activity is quiescent, is mainly dependent upon hormonal local effect played by estrogen compounds on the HEM of the male patients. In this sex, in fact, whose tissues are not usually adapted to an estrogen action, the effect of estrogens on a responsive tissue such as the newly-vascularized HEM could lead to an increased formation of tissue Plasminogen Activator (t-PA), a compound that, escaping into the subdural collection, could maintain a local hyperfibrinolysis with formation of Fibrinogen Degradation Products (FDP). Therefore local hyperfibrinolysis enhanced by steroid hormones and the subsequent CSDH may perhaps be influenced by the prophylactic or adjuvant treatment with inhibitors either of the aromatase activity or of the estrogen action at receptor level.


Power at meetings: strategies to move people. Opportunities exist during meetings to become visible, make impressions, gain control, and be an initiator of decisions. Selective strategies and group dynamic skills enhance the nurse manager's ability to generate influence and power at meetings.


Intracranial hydatid cysts: experience with surgical treatment in 120 patients. Intracranial hydatid cysts, although rare, are still prevalent in agricultural and sheep-raising communities. The authors discuss some of the peculiarities in 120 consecutive cases of intracranial hydatid cysts and review the literature in this report.


Gadolinium-DTPA enhancement of dural structures on MRI after surgery. Gadolinium-DTPA enhanced MRI was examined before and after surgery in 14 patients with particular attention to the enhancement of falx cerebri, tentorium cerebelli and dura mater. A marked enhancement was observed in 2 falx and 2 tentorium before surgery, whereas it was observed in 7 falx, 9 tentorium and 11 dura after surgery. Among 6 falx, 7 tentorium and 12 dura showing increased enhancement after surgery, 2 falx, 3 tentorium and 8 dura showed marked enhancement which was not observed before surgery. A small amount of subdural haemorrhage during surgery is known to heal as subdural neomembrane with capillaries. An increased enhancement of dural structures conceivably derives from the extravasation of Gd-DTPA through capillaries involved in the subdural neomembrane. In the postoperative MRI, the enhancement of dural structures should be taken into consideration.


Metallic fragment embolization to the middle cerebral artery. A 25-year-old male was wounded accidentally in the neck by a metallic fragment, which penetrated his right carotid artery and migrated within the ipsilateral middle cerebral artery. Clinical and laboratory findings over a 16-month-period are reported. Problems arising from the presence of metallic emboli to the cerebral circulation are discussed on the basis of the pertinent literature.


Extrusion of peritoneal catheter through a thoracic skin fistula: report of a rare complication of ventriculoperitoneal shunt. A very rare complication of ventriculoperitoneal shunt is presented. The tip of the distal catheter extruded through a skin fistula in the right subclavian region. After the replacement of a new catheter in the peritoneal cavity, inflammation of the overlying scar occurred. Then, a ventriculoatrial shunt was carried out. The authors suggest a possible mechanism of this complication.


Fibrous dysplasia of the cervical spine with atlanto-axial dislocation. We report on a case of fibrous dysplasia of the cervical spine accompanied by atlanto-axial dislocation, a rare condition first reported by Stirrat. A 37-year-old man who had shown cervical myelopathy for about 6 months was diagnosed as having cervical fibrous dysplasia on the basis of plain x-ray and CT film findings. In addition, atlanto-axial dislocation, which was the apparent main cause of his symptoms, was also detected. We performed a successful two-stage operation from first the posterior and then the anterior approach. The possibility that grafted cancellous bone for anterior fusion may be replaced by dysraphic tissue in the presence of fibrous dysplasia was a complicating factor in this case.


Convexity meningioma associated with empty sella presenting as primary amenorrhea. A case of a 30-year-old female seen for a convexity meningioma is presented. History and investigations revealed an empty sella turcica associated with primary amenorrhea. The removal of the convexity meningioma resulted in the disappearance of the amenorrhea and in the rise of plasma gonadotropins. The importance of the consideration of intracranial causes in patients who have a delayed puberty or the absence of a menstrual history is briefly emphasized in the light of literature.


Vasospasm after experimentally induced subarachnoid haemorrhage and treatment with nimodipine. At day one and on the following day subarachnoid haemorrhage (SAH) was induced in SPF-rats by injection of a mixture of autologous blood and CSF into the cisterna magna. At day eight the animals were treated with Nimodipine. Extracellular calcium and -potassium concentrations as well as local cerebral blood flow and arterial blood pressure were measured simultaneously. The cerebral vasospasm was documented by corrosion casts. The control group underwent the same procedure without previous SAH. Cerebral vasospasm still exists after nimodipine infusion as it can be demonstrated by corrosion casts showing an intensive grooving and a vertical relief. Extracellular potassium and calcium concentration are higher in the SAH-group than in the control-group. The influence of nimodipine to blood pressure and cerebral blood flow is more impressive in rats with SAH showing a significant decrease in blood pressure and local blood flow.


Acetylcholinesterase-rich pyramidal neurons in Alzheimer's disease. The distribution of acetylcholinesterase (AChE)-rich pyramidal neurons was studied in the cortices of 7 Alzheimer's Disease (AD) patients and 4 normal-aged subjects. Both groups showed a characteristic distribution of these neurons with the highest density in motor and premotor areas, moderate density in association cortices, and low density in limbic-paralimbic areas. Three areas (Brodmann areas 6,22, and 24) were chosen for quantitative analysis. The number of pyramidal neurons that display an AChE-rich staining pattern was significantly reduced in AD patients. Nerve cell density was not significantly different in adjacent Nissl-stained sections. The density of AChE-rich (cholinergic) fibers was also decreased in all three cortical areas of the AD patients but was not correlated with the number of AChE-rich neurons. Loss of AChE-rich neurons was more pronounced in areas with high counts of tangles. These findings show that layer 3 and 5 pyramidal neurons in AD display a reduction of AChE activity. This phenomenon can not be attributed to the well known loss of cortical neurons or cholinergic innervation in AD.


Cell loss in the nucleus raphes dorsalis in Alzheimer's disease. Marked neuron loss in the predominantly serotonergic nucleus raphes dorsalis (NRd) in Alzheimer's disease (AD) has repeatedly been reported in the literature. However, most of these studies quantitated only part of the NRd and data were expressed as numerical density. Applying a 3-dimensional sampling scheme throughout the entire rostrocaudal extent of the NRd and sampling neurons regardless of their size and staining characteristics, an overall neuron loss of 39.4% was demonstrated and a tendency for cell shrinkage was likely to be present. No rostrocaudal gradient in neuron loss could be shown. These NRd data are in accordance with neuron loss in other subcortical structures in AD.


Olfactory bulb lesions in Alzheimer's disease. The olfactory bulb (OB), with its comparatively simple and well-delineated connectivity, presents an interesting system for examining cell-specific pathology in neurologic degenerative disorders such as Alzheimer's disease (AD). We have found that in AD the large, efferently projecting neurons (mitral cells) of the OB degenerate, typically without classical Alzheimer neurofibrillary changes. In some cases, with less severe neocortical pathology, the terminal arborizations of olfactory nerve appear hyperplastic and are associated with focal accumulations of A-4 (beta-amyloid) immunoreactivity that are not detectable by standard amyloid stains. These abnormalities may represent a pathologic manifestation of normally occurring plasticity in the olfactory system.


Impaired acquisition of novel locomotor tasks in aged and norepinephrine-depleted F344 rats. Performance of rats on a motor learning paradigm that has been demonstrated to be dependent upon cerebellar norepinephrine (NE) was studied in 20-month-old F344 rats. The behavioral task is identical to that described by Watson and McElligott: Rats are trained on a runway consisting of aluminum pegs arranged in a regular pattern. Rats receive a water reward at either end of the runway. Subsequent to training, rats are tested for running times on a runway with irregularly spaced rods. The ability of rats to improve their performance (decrease their running times) on this novel motor task is diminished in young rats that have received 6-hydroxydopamine lesions. Rats at 20 months of age are known to have deficits in cerebellar noradrenergic transmission; thus, the hypothesis to be tested was to determine if aged rats demonstrated performance deficits similar to young rats depleted of central stores of NE. The rate of acquisition of the task was determined by the decrease in running times with successive days of training. The ability of 20-month-old F344 rats to acquire proficiency on the novel motor task was impaired and the rate of acquisition of the novel motor task was not different from the young 6-hydroxydopamine-lesioned rats. In an attempt to distinguish between alterations in motor coordination and motor learning, additional tests of psychomotor performance were assessed for all groups of rats. These tests included a walking on 2.5- and 5-cm rods, speed of running on the motor task, and number and types of mistakes made on the motor learning task.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of Con A-binding glycoproteins in synaptosomal membranes. Concanavalin A (Con A)-binding proteins obtained from solubilized synaptosomal membranes of bovine brain were analyzed by two-dimensional electrophoresis (2DE), and were identified by peroxidase conjugated Con A (Con A-peroxidase staining), after transfer from 2DE gel to nitrocellulose paper. The Con A-binding proteins were resolved up to 40 spots, ranging in isoelectric points (pI) from 4.5 to 8.0 and molecular weight (MW) from 10 kDa to 120 kDa. Most of the Con A-binding proteins were streaked across a pH gradient and/or exhibited as multiple spots, indicating broad charge and molecular weight heterogeneity. The presence of protein groups that showed high affinities for Con A were revealed. Most interesting group (named GP51), which consisted of seven spots separated horizontally in charge heterogeneity (pI5.85-7.5) with MW 51 kDa, was characterized by its binding to an immobilized protein A gel. This implies that GP51 is related to immunoglobulins and/or GP51 may be a new member of the immunoglobulin supergene family.


Reduced temporal lobe blood flow in Alzheimer's disease. We used single photon emission computed tomography with the blood flow tracer [123I]N-isopropyl-p-iodoamphetamine (IMP) to study regional cerebral blood flow (rCBF) in 50 mildly and moderately demented Alzheimer's disease (AD) patients to evaluate rCBF as a function of disease severity. Relative rCBF (normalized to occipital cortex) was significantly lower than controls in temporal cortex for both mildly and moderately demented patients. Similar numbers of patients in both groups demonstrated perfusion abnormalities in temporal neocortex. Parietal cortex was more variably involved with greater numbers of moderately than mildly demented patients showing perfusion abnormalities. Relative rCBF in dirsolateral frontal cortex was reduced only in the moderately demented patients. Disease severity, as measured by the Mini Mental Status Examination, was associated with relative rCBF only in dorsolateral frontal and parietal cortex. These results suggest that the temporal lobes are the first neocortical regions affected by AD and that other cortical areas become involved as the disease progresses.


Microcephalic cerebrum with hypomyelination in the congenital goiter mouse (cog). 2',3'-Cyclic nucleotide 3'-phosphohydrolase activity in the cerebrum of the congenital goiter mouse (cog/cog) is reduced in comparison with the normal heterozygote (cog/+). The weight of the cog/cog cerebrum and cerebellum were significantly less than those of the normal controls, 89.0% less for the cerebrum, and 81.1% less for the cerebellum. However, no differences were observed with regard to DNA and RNA content and the RNA/DNA ratio. The results of this study indicate that hypomyelination in the congenital goiter mouse is restricted to the cerebrum, and is not related to arrested glial proliferation.


Changes in intraneuronal lipopigment in Alzheimer's disease. Brains were examined from 22 patients with Alzheimer's disease (AD) (mean age 80.5, S.D. 11.5) and were compared with brains from 20 nondiseased subjects (mean age 81.1, S.D. 10.2). Intraneuronal lipopigment in all layers of a region of the superior frontal cortex was identified by fluorescence microscopy. The areas enclosed by the outlines of discrete regions of lipopigment autofluorescence were measured and assigned to a range of size categories. AD was associated with significant (p less than 0.05) decreases in the mean number (per neuron) of discrete regions of yellow lipopigment autofluorescence in the three smallest size categories and a significant increase in one of the larger size categories. Also, AD was associated with a significant decrease in the mean number (per neuron) of discrete regions of lipopigment autofluorescence (p less than 0.001). Significant (p less than 0.05) correlations were obtained between the Blessed dementia score (obtained within 2 years of death) and these lipopigment variables. The changes in neuronal lipopigment in AD may reflect an increased rate of lipopigment formation related to membrane and lysosomal abnormalities.


Age-related changes in sulfide-silver staining in the rat neostriatum: a quantitative histochemical study. The density and distribution of sulfide-silver staining in the neostriatum of 3-, 12-, and 24-month-old male Sprague-Dawley rats were analyzed using the neo-Timm sulfide-silver histochemical technique associated with microdensitometry. This technique stains zinc-containing terminals in the striatum and the density of neo-Timm staining is considered to be parallel to the density of synaptic boutons containing zinc. In the neostriatum sulfide-silver, staining was intense in the matrix, although the striosomes did not show appreciable reactivity. The density of sulfide-silver staining was significantly reduced (p less than 0.001) in the matrix of 12-month-old in comparison to 3-month-old rats. No further changes were noticeable between 24- and 12-month-old rats. In contrast, the area and the perimeter of neostriatum that were assessed by quantitative image analysis did not show age-related changes. The present results indicated that similar to the observations for a variety of neurochemical parameters of rat neostriatum such as local cerebral glucose utilization, cholinergic muscarinic receptors, and dopamine D-1 receptors, zinc-containing striatal terminal were primarily decreased between young and adult subjects but not between adult and aged animals.


A factor derived from chick embryo retina which inhibits DNA synthesis of retina itself. Chick embryo retinas contain a peptide factor that inhibits DNA synthesis in explants of chick embryo retina. The inhibitory factor, obtained by acid/ethanol extraction from 15-day-old chick embryo retinas, was partially purified by affinity chromatography on heparin-sepharose CL-6B and gel filtration on Sephadex G-100. The inhibitor reduced DNA synthesis with maximal effects observed in retinal explants from 7 to 8-day-old chick embryos. The inhibitory effect became apparent after 10 h of incubation and reached the maximum levels after 16 h. DNA-inhibiting activity was heat and acid-stable and was destroyed by trypsin and alkaline treatments. The inhibitory effect was observed in retinal explants incubated in a medium free from L-glutamine, and the addition of this compound to the medium reduced the inhibitory effect in a concentration-dependent manner.


The susceptibility of MAP-2 to proteolytic degradation increases when bound to tubulin. During experiments studying dietary effects on phosphorylation/dephosphorylation of MAP-2 we found that incubation of microtubules with alkaline phosphatase resulted in extensive proteolysis of MAP-2 but not of tubulin or Tau proteins. In the absence of tubulin, when microtubule-associated proteins (MAPs) were incubated with alkaline phosphatase, MAP-2 was not proteolyzed. This suggests that binding to tubulin induces a conformational change in MAP-2 which makes it more susceptible to proteolysis. The proteolysis of MAP-2 by alkaline phosphatase was prevented by inhibitors of serine proteases, suggesting that the commercial preparation of the enzyme is contaminated by a serine protease and/or that the enzyme also has a weaker proteolytic activity. In addition, selective proteolysis of MAP-2 can be obtained with the metalloprotease collagenase. Brain homogenates are shown to contain a Ca(2+)-dependent protease which selectively degrades MAP-2 bound to tubulin. These results suggest that selective proteolysis of tubulin-bound MAP-2 could play a role in the regulation of microtubule dynamics in response to extracellular signals.


Decreased carbachol-stimulated inositol 1,3,4,5-tetrakisphosphate formation in senescent rat cerebral cortical slices. It is well established that muscarinic cholinergic receptors are linked to phosphoinositide hydrolysis in brain. Previous studies of muscarinic responses used Li+ to increase inositol phosphate accumulation and suggested little or no change during aging. Li+ disrupts certain aspects of the inositol phosphate metabolism and inhibits the formation of inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. Ins(1,3,4,5)P4 appears to have second messenger functions. To investigate the effects of aging on agonist stimulated Ins(1,3,4,5)P4 formation, young (6-8 months) and old (28-30 months) Fischer 344 rat cerebral cortical or hippocampal slices were challenged with various agonists known to stimulate phosphoinositide hydrolysis in brain using a recently developed assay that does not use Li+. Carbachol and quisqualate stimulated [3H]inositol trisphosphate ([3H]InsP3) and [3H]Ins(1,3,4,5)P4 formation in young and old rat cerebral cortical slices. Norepinephrine, 5-hydroxytryptamine, and vasopressin failed to stimulate [3H]Ins(1,3,4,5)P4 or [3H]InsP3 formation in either young or old rat cerebral cortical slices. In old rat cerebral cortical slices, the carbachol-stimulated [3H]Ins(1,3,4,5)P4 formation was reduced by 44%. Angiotensin II stimulated [3H]InsP3 was increased (219%) in old rats. There was no influence of aging either on the basal level or on the maximal response to carbachol or quisqualate in hippocampal slices. These studies suggest region-specific changes in phosphoinositide hydrolysis during aging.


Regional alterations in brain amino acids during the estrous cycle of the rat. Concentrations of 11 amino acids, including the neurotransmitters GABA, glutamate, aspartate, glycine and taurine, were determined in 12 brain regions of female rats during different stages of the estrous cycle. In addition, amino acids and sex hormone levels were determined in plasma. All sample collections were done in the forenoon between 9 and 11 a.m. Most regional amino acid levels measured did not change significantly during estrous cycle, but significant alterations were found for GABA and glutamate in hypothalamus. Both amino acids were slightly decreased in hypothalamus during proestrus, which might reflect an alteration of GABA turnover in response to the high estrogen levels during this stage. A decreased glutamate level during proestrus was also found in thalamus, while both glutamate and GABA did not vary throughout estrous cycle in any of the other examined regions, including substantia nigra, amygdala, striatum, cortex and hippocampus. When diestrus was subdivided according to progesterone levels, high levels of this hormone seemed to be associated with effects on metabolism of certain amino acids, including glycine in substantia nigra, alanine in thalamus and threonine in pons/medulla. However, the few changes in regional amino acid concentrations found during the estrous cycle were so small that the functional significance of these changes cannot be ascertained without further determination of the cellular or subcellular compartments of brain tissue involved.


Ventricular injection of nerve growth factor increases dopamine content in the striata of MPTP-treated mice. Experimental depletion of dopaminergic striatal neurons was induced in mice with the neurotoxin MPTP. To investigate a possible effect of nerve growth factor on the damaged neurons, we injected 4 micrograms into the right cerebral ventricle of mice three days after the last administration of MPTP. We found a significant increase of dopamine and homovanillic acid in the striatum of MPTP treated mice after NGF administration when compared with dopamine and HVA levels in MPTP-treated control mice (p less than 0.001). The increase of dopamine and homovanillic acid seems to be related to a partial restorative effect of NGF on the damaged dopaminergic cells, since ventricular administration of NGF to normal mice did not increase dopamine or homovanillic acid contents above the levels measured in untreated controls. It appears that administration of nerve growth factor produces a beneficial effect on damaged dopaminergic neurons; this effect could be due to stimulation of neuron sprouting from neurons that survived the toxic effect of MPTP. The increase of dopamine levels was seen 8 days after injection of nerve growth factor and was maintained at least until day 25, showing a lasting persistence of the restorative effect.


[3H]serotonin binding sites in goldfish retinal membranes. Serotonin (5HT) binding sites were studied in goldfish retinal membranes by radioligand experiments. The binding site of [3H]5HT was sensitive to pre-treatment of the membranes at 40 degrees or 60 degrees C. 5HT and 5-methoxy-N,N-dimethyltryptamine were the best inhibitors of [3H]5HT binding to retinal membranes. The 5HT2 agonist, 1-(-naphthyl)piperazine, was also a potent inhibitor, however, (+)-1-2,5-dimethoxy-4-iodophenyl-2-aminopropane was less efficient. The catecholaminergic agents haloperidol and clonidine did not display an important inhibition. Propranolol, also reported as 5HT1B antagonist, was a relatively potent blocker. Monoamine uptake blockers did not show potent inhibition. The GTP analog, GppNHp, inhibited the binding. The iterative analysis of saturation curves revealed two classes of binding sites, a high affinity component (B(max) 2.45 pmol/mg of protein, kd 6.86 nM), and a low affinity component (B(max) 53.46 pmol/mg of protein, Kd 232.07 nM). Analysis of the association and dissociation kinetics suggested a binding site (Kd 2 nM). The semilogarithmic plot of the dissociation kinetics gave curves concave to the upper side. The selectivity of the binding and the inhibition by GppNHp suggest the existence of 5HT1 receptors in goldfish retina. The low affinity interaction probably represents the transporter of 5HT or a subtype of receptor expressed in glial cells.


[Experience with BALT magic catheter (PURSIL catheter); especially investigation about advantage, disadvantage and the applications]. BALT magic catheter (PURSIL catheter) is a new catheter which is more flexible and plaint than the TRACKER-18 catheter because its mid-section and distal portion are made from polyurethane and silicon rather than polyethylene. Because the PURSIL catheter is flexible, it cannot be inserted with a guide wire, although it can be inserted into circulation during injection of contrast medium. Its inner diameter, 3.5mm, is smaller than that (5mm) of the TRACKER. There are few reports of embolization with the PURSIL catheter, and these describe only embolization using adhesive liquid embolus material. Embolization using small particles through the PURSIL catheter has never been reported. We report the catheterization using the PURSIL catheter of 26 arteries in 15 patients. The catheter was used for superselective angiography to clarify feeder and amytal tests in 5 patients with AVM, and embolization using PVA particles (150-250 microns) was performed in 1 patient with AVM, 3 patients with dural AVM, 4 cases with meningioma and 1 patient with vertebral aneurysm. Small PVA particles were easily injected without resistance through this catheter. In only one patient with dural AVM, was catheterization with this catheter not successful, and that was because the distal portion of the internal maxillar artery was extremely tortuous because of severe atherosclerosis. No complications associated with the use of this catheter were observed. We think that the greatest advantage of this catheter is the safety afforded by not using a guide wire. A disadvantage of this catheter is that, because of its small inner diameter, only small particles, or liquid embolus material can be injected through it.(ABSTRACT TRUNCATED AT 250 WORDS)


[Inhibition of c-sis protein synthesis and cell growth with antisense oligonucleotides in human glioma cells]. The protein encoded by the proto-oncogene c-sis is over-amplified in human neuroglial tumors and has been hypothesized as playing an important role in tumorigenesis, but this hypothesis remains to be clarified. In order to address this issue, we examined the effect of 18-bp oligodeoxynucleotides complementary to the sense mRNA of c-sis upon glioma cell growth. First, we investigated the expression of c-sis protooncogenes within cultured human glioma cell lines and also fresh glioma specimens by using polymerase chain reaction. We could detect mRNA transcripts of c-sis in 3 out of 4 glioma cell lines (U138MG, U251MG and A172) and two in 5 glioblastoma multiforme specimens. The antisense oligonucleotides complementary to c-sis mRNA were efficiently incorporated into A172 in vitro and the kinetic study showed that maximum uptake occurred after 48 hours of incubation with antisense oligomers. Exposure of human glioma cell lines to antisense oligodeoxynucleotides targeted against first initiation codon inhibited cell proliferation in a time and dose dependent fashion. From the flow cytometric analysis using anti-c-sis sera, it was demonstrated that the antisense oligomers specifically block the de novo synthesis of intracellular c-sis protein by glioma cells dose-dependently. In contrast to this, the corresponding sense oligomers inhibited neither synthesis of c-sis protein nor glioma cell growth. Taken together, these results clearly support a role of c-sis protein in the proliferation process and show that inducible protein expression can be blocked by means of synthetic oligonucleotides complementary to a coding exon.


[Experimental study of aneurysmal occlusion with fibrin glue]. The authors report an experimental trial of intra-aneurysmal occlusion using fibrin glue. Nowadays, with the development of microsurgical techniques and aneurysmal clips, results of direct radical operations have been improving. But quite a few aneurysms cannot be clipped because of their size, location, broad neck etc. Some authors have treated these aneurysms with innovative techniques (detachable balloon techniques etc). In these methods, the occlusive state of the aneurysms is not always obtainable because of the size of their neck. Besides, it is not always possible to preserve the parent arteries of the aneurysms. Experimental aneurysms in cervical carotid arteries of dogs are treated by direct injection with fibrin glue. During its injection, influx of fibrin glue was prevented by occlusion of the aneurysmal orifices with inflated polyethylene angioplastic balloons. The aneurysms which were completely (100%) filled by the injection of fibrin glue (100% infused group) were totally obliterated in 10 (71%) of the 14 cases. The parent arteries were completely preserved in all instances. Follow-up study demonstrated satisfactory maintenance of this occluded state in the aneurysms in the 100% infused group. In completely occluded cases, all aneurysms maintained this state. On the other hand, 1 of the 4 incompletely obliterated aneurysms recanalized partially. These occluded aneurysms were studied by a light microscope (LM) and a scanning electron microscope (SEM). At day 7 after the occluding procedure, the margin of the aneurysmal orifice was covered by a layer of fibroblasts. At day 21, almost half of the aneurysmal cavity had been substituted with connective tissue. The orifice of the aneurysms was covered with an endothelial layer.(ABSTRACT TRUNCATED AT 250 WORDS)


[Craniotomy for lesions in the cerebral convexity; how to precisely localize the lesions with conventional CT slices]. A simple direct precise localization with a CT scan for convexity lesions is presented. The shape of the normal calvarium was analyzed and a characteristic pattern was obtained, that is, one spherical surface in the frontal area and 6 flat planes in the temporal, parietal and occipital areas. The temporal plane is perpendicular to the orbito-meatal line (OML), while the parietal plane declined 29 degrees in the A-P view, and the occipital plane declined 60 degrees in the lateral view. A summit of these three planes forming the parietal tubercle, and the crest following the tubercle between the parietal and occipital planes were detected either by CT scan, or by palpating the skull. Conventional methods of preoperative localization include measurement and calculation from the base line such as OML, or obtaining a CT scan with a marker on the scalp. The former might have an error that will be amplified in the parietal region that would not be negligible. The latter is a rather troublesome method demanding that the CT scan be taken after shaving the hair. Landmarks utilized for the localization should be identified both on the CT scan and on the scalp or skull. These involved OML, coronal suture, parietal tubercle, inion, pineal body, midline and so on. Of these, the coronal suture runs almost perpendicular to the OML and would be the best landmark for the localization in the parietal area.(ABSTRACT TRUNCATED AT 250 WORDS)


[Fresh fracture of the odontoid process treated with direct screw fixation; a case report]. A case of a fresh type II fracture (Anderson & D'Alonzo) of the odontoid process treated with direct screw fixation is reported. A 52-year-old man complained of severe neck pain following a hit on his forehead incurred in a falling accident. Neurological examination was normal. Cervical spine x-ray films and axial CT scans revealed a fracture at the base of the dens. It was slightly oblique leftup and rightdown, and the dens fragment was displaced 3mm lateral to the right. One week after the injury, this odontoid fracture was directly fixed with a compression screw by an anterior cervical approach. Immediately after the operation, his neck pain disappeared. He had only 4 days of bed rest and 2 months of external immobilization with a simple neck collar. He returned to his previous job 2 months after surgery without any limitation of his neck movement. At follow-up examination 16.5 months after the operation, x-ray films demonstrated complete fusion of the fracture and no problem about the screw such as displacement or breakage. Direct screw fixation of an odontoid fracture via a transcervical approach was thought to be a reasonable method of treatment. For proper assembly of this method, the following two points are particularly recommended: a screw insertion perpendicular to the fracture plane and the use of an optimal screw with both the desired total and thread lengths.


[Unilateral agenesis of the internal carotid artery in a patient with ruptured aneurysm of the anterior communicating artery; a case report]. This 27-year-old female suffered from subarachnoid hemorrhage. Angiography revealed a ruptured aneurysm of the anterior communicating artery. Unilateral absence of the right internal carotid artery was also demonstrated angiographically. Both the right anterior and middle cerebral arteries were perfused from the left carotid artery via the anterior communicating artery. Absence of the right carotid canal was proved on bone CT. Neuroradiological difficulties in differential diagnosis between agenesis and aplasia of the internal carotid artery were discussed. Subsequently, a diagnosis of adult type unilateral agenesis of the internal carotid artery with collateral circulation was made. The mechanism of association of cerebral aneurysm in patients with agenesis of the internal carotid artery was also discussed. From our experience, abnormal vascular anatomy should be carefully studied prior to direct surgery for a ruptured aneurysm in patients with unilateral agenesis of the internal carotid artery.


[A case of an cerebello-pontine angle pineoblastoma]. An extremely rare case of a left cerebello-pontine angle (CP angle) pineoblastoma has been reported. The patient was a 32-year-old male whose initial manifestations were those of increased intracranial pressure. CT scan showed a large enhancing mass located at the left CP angle, associated with a moderate occlusive hydrocephalus. Left suboccipital craniectomy was performed. The mass was an extramedullary tumor which had compressed the left cerebellar hemisphere, and was easily separable from the adjacent tissue. The tumor was totally resected, and the patient had a temporary release from the symptoms. Recurrence and spinal dissemination were found within the ensuing few months. The tumor had invaded deeply through the left CP angle into the cerebellar parenchyme, and showed no anatomical connection with the pineal body. The tumor dissemination was also observed widely in the spinal subarachnoid space. No abnormalities at the pineal region were able to be confirmed using CT and MRI studies. Irradiation to the whole brain, to the localized left CP angle and to the spinal cord with additional chemotherapy was given. The patient died half a year after the first operation. Autopsy was not performed. Histopathologically, the tumor was delineated into lobular structures by reticulin fibrils and vimentin-positive interstitial tissue. Tumor cells were small in size, and had irregularly shaped hyperchromatic nuclei with increased mitotic figures, and formed various types of rosettes; pineocytomatous, Flexner-Wintersteiner, Homer-Wright and perivascular. Fine argyrophilic cell processes with club-shaped expansions were demonstrated inside the pineocytomatous rosettes.(ABSTRACT TRUNCATED AT 250 WORDS)


[Bilateral distal anterior cerebral artery aneurysms associated with polycystic kidney and liver disease; a case report]. A patient who had bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease is reported. A 57-year-old woman was referred to our center with headache and disturbance of consciousness. On admission, her level of consciousness as evaluated by the Japan Coma Scale was 10. CT revealed subarachnoid hemorrhage, especially in the interhemispheric fissures. Right carotid angiography demonstrated bilateral distal anterior cerebral artery aneurysms and a right middle cerebral artery aneurysm. All three aneurysms were clipped in a one-stage procedure. The patient was discharged without any neurological deficits two weeks after the operation. Bilateral distal anterior cerebral artery aneurysms are extremely rare. This is the first report of such aneurysms and a right middle cerebral artery aneurysm in association with polycystic kidney and liver disease. The etiology of these aneurysms is discussed.


[Treatment of arteriovenous fistula in the skull base; a case of von Recklinghausen's disease]. We presented a case of neurofibromatosis associated with intractable arteriovenous fistula of the internal carotid artery in the skull base. A 41-year-old man presenting dyspnea and neck swelling was treated with balloon occlusion for arteriovenous fistula. This was followed by its total removal. At operation, we found that arteriovenous fistula was formed by the invasion of the internal carotid arterial wall of a neurofibroma in the skull base, which had been induced by neurofibromatosis. This is a rare case corresponding to vascular neurofibromatosis in the internal carotid artery.


[Rapid resolution of acute subdural hematoma; report of two cases]. We reported two cases of rapid resolution of acute subdural hematoma. Case 1, a 21-year-old female, sustained head trauma and became unconscious for about 15 min. Probably she was suffering from posttraumatic amnesia for about 1 day. On admission J.C.S and G.C.S were 20 and 9 (2 + 2 + 5) points, respectively. Neurological examination showed no abnormalities. An initial computed tomography (CT) scan taken 2 hours after the injury showed a high dense subdural hematoma on the left cerebral hemisphere and hemispheric swelling. She was conservatively treated. A follow up CT scan taken 8 hours after the injury disclosed rapid disappearance of the hematoma and cerebral swelling. Case 2a 23-year-old male, sustained head trauma and became unconscious for about 30 min. On admission J.C.S and G.C.S were 1 and 14 (4 + 4 + 6) points, respectively, and slight right hemiparesis was noted. An initial CT scan taken 2 hours after the injury showed subdural hematoma of the left cerebral hemisphere and hemispheric swelling. He was conservatively treated. A follow up CT scan taken 24 hours after the injury revealed almost complete disappearance of the subdural hematoma and cerebral swelling. It was suggested that the rapid resolution of acute subdural hematoma was attributable to redistribution due to decrease of ICP, and washing out by cerebrospinal fluid.


Impaired PRL response to hyperthermia in alcoholic men. The aim of this study was to evaluate the release of PRL to sauna-induced hyperthermia in 10 chronically alcohol-addicted male subjects after a few weeks of abstinence. In contrast with normal men the alcoholic men showed higher basal levels of PRL and the exposure to hyperthermic stress did not stimulate in PRL secretion. These results indicate that chronic alcohol abuse is associated with functional pituitary alterations similar to other states of addiction.


Preprothyrotropin-releasing hormone mRNA and TRH are present in the rat heart. PreproTRH mRNA has been identified in rat cardiac tissues by Northern analyses and RNase protection assays with a specific rat 32P-TRH cRNA probe. Densitometric analyses revealed that atrial ppTRH mRNA concentrations were approximately five-fold greater than those of the ventricles. TRH concentrations (RIA), by contrast, were two-fold higher in ventricles. These data suggest that TRH and TRH mRNA are present in the rat heart, but their concentrations are dissociated, possibly because of differential post-transcriptional or post-translational processing. TRH is postulated to play an autocrine or paracrine role in cardiac physiology.


Mobilization of calcium from intracellular store as a possible mechanism underlying the anti-opioid effect of angiotensin II. Angiotensin II (AII), injected intracerebroventricularly, has been shown to antagonize opioid analgesia. The mechanism for this was obscure. In the neuroblastoma X glioma NG 108-15 hybrid cell line, the K(+)-induced increase in [Ca2+]i can be suppressed by the delta opioid agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) at 0.01-1 microM, an effect completely reversed by the opioid antagonist naloxone. Angiotensin II (AII) at concentrations of 0.1 and 1 microM mobilized free Ca2+ from an intracellular pool, and this effect was antagonized by the AII receptor antagonist saralasin. All (1 microM) had no significant effect on the increase in [Ca2+]i induced by K+, but it blocked the suppressive effect of DPDPE on the K(+)-induced [Ca2+]i increase. The results indicate that mobilization of intracellular calcium may underlie the anti-opioid effect of AII.


A neurosecretory granule Lys-Arg Ca(2+)-dependent endopeptidase putatively involved in prooxytocin and provasopressin processing. A Ca(2+)-dependent endopeptidase cleaving at the carboxyl side of the paired Lys-Arg residues has been found in the neurosecretory granules of the rat neurointermediate pituitary. The specificity pattern on synthetic fluorogenic substrates, the inhibitor profile, the pH optimum of 5.0 and the Ca(2+)-dependence are compatible with an involvement of this enzyme in the prooxytocin and the provasopressin processing within the granules. The enzymatic features of the neurohypophysial granule endopeptidase resemble those of the insulinoma granule type II endopeptidase and suggest that the same Ca(2+)-dependent protease or closely related enzymes could be involved in processing Lys-Arg-containing prohormones in neuroendocrine cells.


Decreased numbers of cholecystokinin-immunoreactive nerve cells in the cerebral cortex of LEC rats with a hereditary hepatitis. The distribution of CCK-immunoreactive cells was investigated by the indirect fluorescence method in the cerebral cortex of LEC (Long-Evans Cinnamon) rats which have recently been introduced as a model of jaundice and hepatic encephalopathy. Reduction of CCK-immunoreactive nerve cells was observed in the brains of LEC rats with stage III to V hepatic encephalopathy in comparison with the rats without hepatic encephalopathy. These observations were confirmed by counting the CCK-positive nerve cells at magnification x 125. 3 microscopic fields per animal were immunostained and CCK-immunoreactive nerve cells counted. The number of CCK-immunoreactive cells per field was 28.5 +/- 0.7 (mean +/- SEM, n = 5) in rats without hepatic encephalopathy, and 14.1 +/- 2.0 (n = 3) in rats with stage III to V hepatic encephalopathy. Thus, the number of CCK-immunoreactive nerve cells was significantly less in rats with stage III to V hepatic encephalopathy (p less than 0.05). A decrease in CCK-immunoreactive nerve cells was not observed in the rats with stage I or II hepatic encephalopathy. This study shows that there is a relationship between the severity of hepatic encephalopathy and the number of CCK-immunoreactive nerve cells in the cerebral cortex.


Rapid, high-yield isolation of human chromogranin A from chromaffin granules of pheochromocytomas. Chromogranin A (CgA) is a useful probe of human neuroendocrine neoplasia and exocytotic sympathoadrenal activity, but the application of CgA immunoassays has not been widespread because of limited availability of purified human CgA. Here we describe a rapid, high yield isolation of human CgA. After obtaining and lysing pheochromocytoma chromaffin granules, the soluble core proteins (chromogranins) were depleted of dopamine-beta-hydroxylase by passage over a concanavalin A-Sepharose affinity column, then lyophilized, resuspended in volatile buffer, and gel filtered on Sephacryl S-300. SDS-PAGE-analyzed column fractions contained homogeneous human CgA, which was verified structurally (N-terminal amino acid sequence) and immunologically (radioimmunoassay and immunoblot). The overall 22.6 mg yield of purified CgA represented 5.7% of the starting vesicle core protein. This preparation will be useful in evaluating the sympathoadrenal system and endocrine neoplasia in man.


A neuropharmacological analysis of compensatory-restorative processes in organic deficit of the parafascicular complex of the thalamus. It has been demonstrated in freely behaving cats, on the basis of a model of the biological precursors of concrete and abstract thinking, that, in the presence of a neurosurgical lesion of various divisions of the parafascicular complex of the thalamus, the restoration of disturbed functions by neuropharmacological agents through an effect on dopamine-, choline-, and GABAergic systems is possible. There is specialization in the neurochemical pathways of the lateral and medial regions of the complex, which opens the possibility of the topical correction of psychopathology of the thalamic level.


Intercentral relationships of cortical bioelectrical activity of the human brain following operative interventions in brainstem structures. The dynamics of the total bioelectrical activity and the parameters of its intercentral interaction was investigated in 52 neurosurgical patients with a focal lesion at the level of the brainstem with the aim of analysis of the compensatory neurodynamic reorganizations of the human brain in the early postoperative period. The study was based on the precise verification of the topography of the pathological focus within the limits of the brainstem; on the dynamic clinical-neurological assessment of different variants of the postoperative course; and on a study of the structure of cortical bioelectrical activity based on visual and spectral coherence analysis. The dependance is demonstrated of the compensatory neurodynamic reorganizations of the brain on the character and degree of the stem lesion (transitory, stable, irreversible).


Interactions of motivation and reinforcement during the performance of a simple instrumental reflex by a monkey. The dynamics of the performance of an instrumental task by Macaca rhesus monkeys was investigated in an automated experiment. Three monkeys were trained to complete a movement with a lever in response to a light stimulus. It was demonstrated that the performance of the instrumental reflex by the monkeys is comprised of the alternation of blocks of more or less continuous realizations and pauses between them. The relationship of the intensity of the work of the monkeys to the time from the beginning of the experiment was studied, and a comparison was made of the magnitude of the intensity for the three monkeys. The average intensity of the work of the monkeys within the blocks of continuous realizations is a constant and individual value. The influence of the degree of deprivation and of the delivery of out-of-turn reinforcement on the work of the monkeys was also investigated.


Catalepsy and hyperkinesis induced by the chronic injection of a tetrapeptide into the neostriatum. The influence on behavior of the chronic (over the course of three weeks) injection of leu-enkephalin and its analog, a tetrapeptide, in doses of 5 and 15 micrograms, into the neostriatum was investigated in experiments on rats. Native enkephalin had little effect, but the tetrapeptide in both doses blocked conditioned reflex avoidance behavior and induced a set of complex changes in behavior. Catalepsy with pronounced waxy rigidity of the skeletal musculature was the main element of the pathological behavior. Stereotypical slow movements of the head and forelimbs began to predominate on the second week of the microinjections. Changes in behavior but without catalepsy and hyperkinesis were observed on the following days. It is hypothesized that the phenomena described are associated with reorganizations of neuromediator systems that accompany the chronic influence on the opiate system of the neostriatum. The role of the enkephalinergic system in the genesis of psychomotor deviations is discussed, as well as the possibility of obtaining through the method utilized of models of neurological and psychopathological deviations.


[Hormonal and metabolic response to trauma: physiopathology and therapeutic management]. This article is a review of present knowledge of the hormonal and metabolic responses to trauma and surgery. The factors which may mediate the responses are discussed and the potential value of different therapeutic manipulations are reviewed. The accelerated breakdown of muscle following significant injury is the most characteristic feature of the metabolic response. The magnitude of the muscle wasting that is potentially proportional to the extent of injury, leads to a marked cachexia which could be considered a part of the multiple organ failure. It does seem that the protein loss and the immunodepression which often occurs after major trauma may be important factors in determining morbidity and mortality of the patients. The prevention or the attenuation of the metabolic stress response could be beneficial in improving immunocompetence and minimizing complications after major trauma or surgery so that an earlier return to normal health could be achieved. At present there are few epidemiological data to support this view but it is an attractive concept in the management of a severely ill patients. We are aware that anaesthetic techniques, nutritional support, normothermia and hormonal manipulation can modify part of the hormonal and metabolic response to surgery. The knowledge of all of them and the clinical implications that their use could have, will be helpful to the anaesthesiologists and the Intensive Care physicians in their daily working in the operation theatre, intensive care unit or in the surgical ward.


Biofeedback control of systemic arterial pressure. The central mechanisms and possibilities of biofeedback of the systemic arterial pressure have been investigated in experiments on cats, rabbits, and rats. The adaptive processes were followed in association with minimization of electrodermal reinforcement during the development of shifts in relation to the level and bioelectrical structure of the AP, as well as the impulse activity of hypothalamic neurons.


[Transesophageal echo-Doppler in children: the importance of the exact measurement of the aortic diameter and its variations over time for estimating the aortic output]. The purpose of the study was to evaluate a new non invasive system of hemodynamic monitoring. The aortic systolic, diastolic and mean diameter have been measured with eco-TM and the aortic blood flow with pulsed Doppler, in order to obtain the aortic output. The aortic systolic diameter and the derived aortic output were then compared to the corresponding values obtained with CT. Ten healthy children were asked to be explored with CT under general anaesthesia and an oesophageal probe was positioned. The mean aortic diameter value was 7.18 +/- 0.91 mm. The systolic and diastolic aortic diameter was 7.87 +/- 0.91 mm and 6.65 +/- 1 mm respectively. The aortic systolic diameter measured with CT was 8.2 +/- 0.92 mm. Correlation analysis with aortic systolic diameter with eco TM as the dependent variable and aortic systolic diameter with CT as the independent variable revealed a highly significant correlation (r = 0.95, coefficient of determination 0.90). The mean percentage difference between systolic and diastolic diameter measured with TM eco scan was 15% with maximum variation 22% and minimum of 10% (p less than 0.003). The aortic blood flow calculated from the systolic aortic diameter was 29% higher than that obtained from diastolic aortic diameter. This would suggest that the correct measurement of the aortic diameter has to be considered in the final evaluation of aortic output especially in children in whom the elasticity of the aortic wall represents a major factor in determining fluctuations of aortic diameter.


[Hypoxemia after heart surgery. An exception or a normal development?]. The course of respiratory exchange through arterial blood gas analysis after coronary bypass-grafting and valvular replacement has been investigated in a cohort of 62 patients. Arterial blood gases were measured at baseline (the day before surgery), and then 1, 2, 3 and 9 days after surgery; in a subset of 18 patients, randomly selected from the same population, pulmonary function tests were also performed at baseline and repeated on day 9. Arterial blood gases showed a remarkable prevalence of hypoxaemia (as defined as arterial PaO2 less than 60 mmHg): 31% on the first, 50% on the second, and 40% on the third post-operative day; anemia and desaturated mixed venous blood were also prominent findings during the first two days. Arterial PO2 resulted higher afterward, although its mean value then was significantly lower than baseline (81.5 +/- 8.8 vs 93.1 +/- 9 mmHg, p less than 0.005). Pulmonary function tests evidenced widespread restrictive changes, with alterated thoraco-pulmonary mechanics (loss of more than 40% of vital capacity and one second forced expiratory flow) and parenchimal lung damage (residual volume and CO diffusion capacity decrease). Some differences in PaO2 course between coronary patients and valvular patients have been releaved; the mean basal PaO2 value of valvular was significantly lower then the other one (86.7 +/- 10.8 vs 94.7 +/- 10.9, p less than 0.05).


Perception of temperature elevation in human seasonal heat adaptation. Higher values of the exponent power function of the perception of temperature elevation (1.66, 1.32, and 1.50) in the summer than in the winter (1.40, 1.08, and 0.84) were established in seasonal investigations in people at room air temperatures of 20, 28, and 40 degrees C. Consequently, following adaptation to the seasonal high temperature a person can feel a smaller temperature increment than in the winter. This suggests a reorganization in the functional activity of the temperature analyzer under the prolonged influence of seasonal high temperature.


Localization of neurons innervating the upper portion of the duodenum in the motor nucleus of the vagus nerve. Using the method of the retrograde axonal transport of horseradish peroxidase and a microelectrode technique, a population of neurons sending axons to the upper portion of the duodenum was identified in the dorsal motor nucleus of the vagus nerve. It was established that the maximal number of such neurons was located 1.0-2.5 mm rostral to the obex. The effects of their stimulation on the electrical activity of the smooth muscles of the duodenum was studied.


[Comparison between propofol and isoflurane in patients undergoing aorto-coronary bypass. Effect on systemic and coronary circulation]. The Authors report their experience with the use of two different anaesthetic techniques (propofol-fentanil versus isoflurane-fentanyl) for induction and maintenance of anaesthesia in patients undergoing coronary artery surgery. Haemodynamic data (regarding systemic and coronary circulation) showed an almost similar pattern of change after induction, intubation, skin incision and sterotomy, except for a greater decrease of systemic vascular resistances after induction in patients who received propofol. Cardiac output decreased more in the isoflurane group while changes in coronary sinus flow were equal in the two groups.


[Alfentanyl and midazolam in combined anesthesia. Clinical evaluation]. We have evaluated the effectiveness of a technique of blended anaesthesia (epidural-general) in 31 patients undergoing major surgery. Thoracic epidural blockade with lidocaina CO2, adrenalin 1/200000, ensures analgesia while induction and hypnosis maintenance were obtained with midazolam, alfentanil, atracurium and N2O/O2. This technique seems able to protect the patients from endotracheal intubation and surgical stress and also to enable a rapid, quiet awakening. The dose of midazolam necessary to maintain hypnosis was inversely proportional to the patient's age. The reversal of hypnosis was necessary in 4 patients only.


[Long-term sedation with propofol in ICU: hemocoagulation problems]. The Authors have studied the effects of propofol on coagulation in 15 patients admitted to ICU. Propofol was used for long-term sedation (therapeutic range 3 mg/kg/h). Variables monitored included: platelets, PTT, PT, Fibrinogen, FDP, AT III. The effects on coagulation has been investigated in three groups of patients: group I) 5 patients that received propofol for 1-3 days; group II) 5 patients that received propofol for 4-10 days; group III) 5 patients that received propofol for 11-35 days. No difference were found about blood coagulation in this groups of patients before and after administration of propofol.


[Effects of propofol and isoflurane on the neuromuscular block induced by atracurium]. Speed of onset, duration of action and recovery time for a bolus injection of atracurium were measured in two groups of patients. In group I anaesthesia considered of propofol, fentanyl, nitrous oxide and oxygen mixture. The induction dose of propofol was 2 mg/kg-1 followed by an infusion of 9.0 mg/kg-1/h-1 for first half hour and 4.5 mg/Kg-1/h-1 subsequently. In group II anaesthesia consisted of isoflurane, fentanyl, nitrous oxide and oxygen mixture. Isoflurane was given upon clinical needs. Speed of onset, duration of action, and recovery time for atracurium were measured in the two groups. No statistically significant differences between speed of onset and duration of action between the two groups were found. The recovery period from T1 = 10% to T1 = 70% twitch response was considerably longer with isoflurane (25 min +/- 6) than with propofol (18 min +/- 3) (p less than 0.01). Results obtained suggest that for adequate relaxation during tracheal intubation smaller doses of atracurium are not needed during isoflurane than propofol administration. Because of the longer recovery period of residual neuromuscular blockade during isoflurane anaesthesia decreasing doses of atracurium and careful monitoring of twitch depression tension are also suggested.


[Thoraco-abdominal binding in the treatment of overdistention of the lung bases in children]. In the patient with homogeneously or inhomogeneously distributed atelectasis, localized primarily in the apices, overdistension of the non-dependent portion of the lung bases, only partially surrounded by the rib cage, is generally observed during mechanical ventilation. This phenomenon is even more pronounced in the neonate and in the infant because their rib cage compliance is almost infinite. In order to protect the lung bases in the event of their overdistension and/or to reexpand the atelectasis of the upper lobes we apply an external resistance, in form of thoracoabdominal binding, to limit the movement of the diaphragm. The degree of the binding's tension is regulated according to the degree of the distension of the lung bases detected on chest x-ray. This restriction was so far applied in 12 children using elastic bandages. We have used the thoraco-abdominal binding with good result in the treatment of atelectasis of the upper lobes, in extensive atelectasis as well as in the treatment of primitive lung bases overdistension, as described in 3 cases reports. We suggest this technique in order to obtain an homogeneous ventilation along the longitudinal axis of the lung. This method does not interfere with prone-supine postural changes, systematically applied in our department, and therefore, the homogeneous ventilation along the vertical axis is also provided.


[Multiorgan damage in exertion heatstroke]. The paper reports a fatal case of exertion heat stroke. The etiopathogenetic, clinical and therapeutic aspects of the case are described; although rarely observed, this pathology must be taken into account by the intensive care unit in order to ensure rapid aid and treatment in an attempt to modify the severe prognosis due to multiorgan damage which increases with the intensity and duration of hyperthermia.


[The external jugular vein course as surface landmark in subclavian perivascular block]. A study of 88 orthopaedic patients undergoing upper limb surgery, was carried out using the external jugular vein as surface landmark of the brachial plexus in subclavian perivascular technique. A significant statistical relationship was found between the insertion point of the needle, relatively to the external jugular vein course, and the block outcome. The best results were observed when the needle was inserted on the postero-lateral side of the vein or when the insertion point coincided with the vein course. Worse results were obtained by foreward insertion. So the external jugular vein could be used as surface landmark to improve the plexus localization in the subclavian perivascular technique of brachial plexus anaesthesia.


[A new approach to the brachial plexus]. In order to avoid complications such as pneumothorax or subarachnoid injection, the paper proposes a new approach to brachial plexus using a supraclavear route based on the pulse of the subclavian artery and 7th cervical vertebra. Complications are unlikely using this route.


[Changes in the plasma amino acid profile in critically ill patients during total parenteral therapy]. The aim of this study was to evaluate the kinetics of arterial plasma amino acid profile during the first 48 h of clinical TPN in order to assess the time necessary to reach the steady-state condition during infusion. Each patient was treated with one of three different amino acid solutions yielding, in the same nitrogen intake, different intakes of individual amino acids. We found four different kinetics for the administered amino acids: an increase of plasma levels immediately after the start of the TPN with no variations during the steady period; the same trend with the steady-state obtained after 6-24 h of TPN infusion; no influence at all; a decrease of fasting plasma levels with the steady-state attained variably during the study period. Each given amino acid showed a different trend partly depending on the supply, suggesting that the steady-state was reached sooner for most amino acids, when the supply was larger. With lower intakes, plasma levels were unaffected or decreased. We conclude that in critically ill patients at least 24 h are needed to obtain stable arterial plasma amino acid concentration during TPN with adequate intakes of amino acid. Knowledge offers the possibility for a quick and accurate assessment of the adequacy of a given preparation (tailored for critically ill patients), it reduces the time span of the study and, as a consequence, the influence of varied metabolic conditions.