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Social class and risk of Hodgkin's disease in young-adult women in 1988-94.

Hodgkin's disease (HD) risk in young adults has been associated with higher childhood social class. Although recent decades have witnessed increases in both young-adult HD incidence rates and the socioeconomic affluence reported to influence risk, social class risk factors have not been reexamined. For 204 cases and 254 controls aged 19-44 years from a population-based case-control study of HD diagnosed in 1988-94 in San Francisco area females, we evaluated social class predictors of HD overall and for subgroups defined by age and by ethnicity. HD was associated weakly with a few childhood social class markers but more strongly with combinations of these variables. Risk was higher for women with family-owned than rented childhood homes; for US-born women with single vs. shared bedrooms at age 11; and for women with 2+ births who were from smaller than larger childhood households. These patterns differed by age, with risk appearing to increase over the young-adult years for some factors and to decrease for others. In whites, risk was additionally associated with having a single childhood bedroom in larger households, and with tall adult height in women from smaller childhood households. In nonwhites, risk was higher for single bedrooms at age 11 in smaller childhood households, taller height and higher maternal education. Most study findings support the hypothesis that HD development in young adults follows protection from early exposure to other children. Variation in risk by age suggests differing etiologies across young adulthood, or the importance of birth cohort-appropriate social-class measures. Negative findings for previously reported risk factors may reflect their insufficient heterogeneity of exposure or their failure to measure cohort-relevant exposures in this population.

Adolescent↗

Salutogenic childhood factors reported by middle-aged individuals. Follow-up of the children from the Lundby study grown up in families experiencing three or more childhood psychiatric risk factors.

This study is salutogenic (= causes of health), focusing on factors which corresponded to good mental health in subjects who had been exposed to at least three child psychiatric risk factors when growing up. The material was drawn from a prospective, longitudinal population study on mental health, the Lundby Study, which was performed in three waves in 1947, 1957 and 1972. In 1988/89, 148 individuals then 42-56 years of age, were re-visited and interviewed about their life span experiences. Factors previously found to increase stress resilience in children and adolescents were identified. The personal dispositions during childhood found to be associated with adult positive mental health were childhood positive self-esteem, successful coping, internal locus of control and intellectual capacity. Childhood family factors, such as trusting relations with a parent and shared values, were also important. Antonovsky's sense of coherence model can be used to explain the mechanisms by which the different variables can lead to health through increasing an individual's capacity for comprehensibility, manageability and meaningfulness, the three concepts of sense of coherence.

Adaptation, Psychological↗

Phenytoin covalent binding and embryopathy in mouse embryos co-cultured with maternal hepatocytes from mouse, rat, and rabbit.

The anticonvulsant drug phenytoin is teratogenic in a variety of species including humans. Traditional embryo culture studies have employed the addition of 9000 g supernatant (S-9) or microsomal fractions from induced rat or mouse liver as an exogenous bioactivating system to approximate a maternal contribution. However, cellular fractions, unlike cultured intact hepatocytes, may themselves be embryotoxic, and do not reflect the in vivo balance of bioactivation and detoxification. To evaluate in vitro the known in vivo differential species susceptibility to phenytoin teratogenesis, day 9.5 (day of plug = day 1) mouse embryos either were cultured alone for 24 hr or were co-cultured with hepatocytes from maternal mice, rats or male rabbits, thereby exposing the embryos to the effects of potential species-specific phenytoin metabolism. In the absence of hepatocytes, phenytoin embryotoxicity was concentration dependent (0, 10, 20 and 60 micrograms/mL), with decreases in embryonic growth, reflected by reduced yolk sac diameter and crown rump length, apparent within the maternal therapeutic range (20 micrograms/mL). Covalent binding of the radiolabeled drug to live embryonic tissue was significantly higher than in control embryos previously killed by fixation, suggesting that the embryo can bioactivate phenytoin to a toxic reactive intermediate. Mouse embryos grew equally well with hepatocytes from all three species, indicating interspecies tissue compatibility. The addition of rat and rabbit hepatocytes, but not mouse hepatocytes, significantly enhanced the phenytoin-induced impairment of mouse embryonic development, as demonstrated by reductions in somite number. The phenytoin-induced impairment of mouse embryonic growth was not enhanced by the addition of rat or rabbit hepatocytes, while mouse hepatocytes conferred protection. The covalent binding of phenytoin to extracellular proteins in the culture medium was not enhanced by the addition of mouse hepatocytes. These results suggest that mouse embryos intrinsically can bioactivate phenytoin to a toxic reactive intermediate, with embryopathic consequences. The protection conferred by maternal mouse hepatocytes suggests a species-specific maternal biochemical balance favouring detoxification that is not shared by rat and rabbit hepatocytes, which enhanced phenytoin embryopathy. Thus, while phenytoin teratogenicity likely involves embryonic bioactivation, maternal determinants may contribute variably to teratologic susceptibility in a species-specific manner.

Animals↗

Tuning the mechanical stability of fibronectin type III modules through sequence variations.

Cells can switch the functional states of extracellular matrix proteins by stretching them while exerting mechanical force. Using steered molecular dynamics, we investigated how the mechanical stability of FnIII modules from the cell adhesion protein fibronectin is affected by natural variations in their amino acid sequences. Despite remarkably similar tertiary structures, FnIII modules share low sequence homology. Conversely, the sequence homology for the same FnIII module across multiple species is notably higher, suggesting that sequence variability is functionally significant. Our studies find that the mechanical stability of FnIII modules can be tuned through substitutions of just a few key amino acids by altering access of water molecules to hydrogen bonds that break early in the unfolding pathway. Furthermore, the FnIII hierarchy of mechanical unfolding can be changed by environmental conditions, such as pH for FnIII10, or by forming complexes with other molecules, such as heparin binding to FnIII13.

Amino Acid Sequence↗

The clinical spectrum of migraine.

The variable clinical features of migraine and some relationships of migraine with other headache disorders have been reviewed. Although these views generally are shared by most headache specialists, some respected headache investigators reject the concept of a spectrum of migraine and conclude that the continuum model is an artifact.

Diagnosis, Differential↗

Variability in the clinical skills of residents entering training programs in surgery.

BACKGROUND: Residents may have significant differences in clinical skills at the start of their surgical training. The purpose of this study was to investigate the variability in these skills by using an objective structured clinical examination. METHODS: A needs assessment was performed, and an objective structured clinical examination composed of 10, two-part stations was developed. Standardized patients (SPs) were trained, validated, and used as both simulated patients and evaluators to assess history taking, physical examination, and interpersonal skills of 10 first-year surgical residents. Structured patient notes (PNs) written by residents after the SP encounters were used to assess history and physical examination documentation skills. Data from one station were not used because more than 25% of the SP ratings were missing. RESULTS: The alpha-reliability was 0.78 for SP ratings, 0.91 for PN scores, and 0.91 for the combined scores. ANOVA revealed significant variation in individual residents' clinical skills as assessed by SPs (F = 4.56, p < 0.01), PNs (F = 11.09, p < 0.001), or both (F = 10.9, p < 0.001). Paired t tests showed that residents scored significantly higher on history taking than on physical examination and attained significantly lower scores on documentation as compared with performance of both history and physical examination (p < 0.001 for each comparison). CONCLUSIONS: The results showed significant variability in clinical skills of the group of residents and yielded detailed information on the performance of each resident. The data were shared with individual residents and are being used to make changes in the educational activities of the program.

Clinical Competence↗

Altered splicing pattern of TACC1 mRNA in gastric cancer.

Transforming acidic coiled-coil (TACC) proteins are centrosome and microtubule-associated proteins that are essential for mitotic spindle function. We identified TACC1 as an immunogenic protein and a potential tumor antigen by applying serological identification of antigens by recombinant expression cloning (SEREX) technique to screen a gastric cancer cDNA library. The 5'RLM-RACE and reverse transcriptase polymerase chain reaction analyses revealed at least six different transcript variants of TACC1 with variable transcription start sites and alternative exon usage (designated TACC1-A-TACC1-F). All transcripts differ in their 5' ends but share an identical 3' region encoding coiled-coil domain. Four transcripts were universally expressed in all normal tissues analyzed but TACC1-D and TACC1-F showed a restricted expression pattern. TACC1-F, a transcript representing the SEREX-identified cDNA clone, was predominantly expressed in brain and gastric tumors to a similar level. TACC1-D was only weakly detectable in kidney and colon but not in other normal tissues, while a relatively strong expression was observed in 50% of gastric cancer tissue samples analyzed. These transcript variants are generated possibly as a result of alterations in efficiency and pattern of alternative splicing; these isoforms may represent genetic markers, for example TACC1-D for gastric cancer. We also propose that inappropriate expression of the isoforms in gastric cancer cells might result in dysfunction of TACC1 thus contributing to the genetic instability.

Alternative Splicing↗

Oxamato-bridged trinuclear NiIICuIINiII complexes: a new (NiIICuIINiII)2 hexanuclear complex and supramolecular structures. Characterization and magnetic properties.

Eight oxamato-bridged heterotrinuclear Ni(II)Cu(II)Ni(II) complexes of formula ([Ni(H(2)O)(dpt)](2)(mu-Cu(H(2)O)(opba)))(ClO(4))2 (1), ([Ni(H(2)O)(dien)](2)(mu-Cu(pba)))(ClO(4))(2).6H(2)O (2), ([Ni(H(2)O)(Medpt)](2)(mu-Cu(OHpba)))(ClO(4))(2).4H(2)O (3), ([Ni(H(2)O)(dien)](2)(mu-Cu(Me(2)pba)))(ClO(4))(2).2.5H(2)O (4), ([Ni(H(2)O)(dpt)](2)(mu-Cu(Me(2)pba)))(ClO(4))(2).2H(2)O (5), ([Ni(H(2)O)(dien)](2)(mu-Cu(OHpba)))(ClO(4))(2).4H(2)O (6), ([Ni(2)(dpt)(2)(mu-Cu(H(2)O)(pba))](2)(mu-N(3))(2))Na(2)(ClO(4))(4).6H(2)O (7), and ([Cu(H(2)O)(2)(dpt)Ni(2)(H(2)O)(dpt)(2)](mu-H(2)Me(2)pba(2-)))(ClO(4))(4).3H(2)O (8) in which opba = o-phenylenbis(oxamato), pba = 1,3-propylenebis(oxamato), OHpba = 2-hydroxy-1,3-propylenebis(oxamato), Me(2)pba = 2,2-dimethyl-1,3-propylenbis(oxamato), dpt = 3,3'-diaminodipropylamine, dien = 2,2'-diaminodiethylamine, and Medpt = 3,3'-diamino-N-methyldipropylamine were synthesized and characterized. The crystal structures of 1, 7, and 8 were solved. For complex 1, the trinuclear entities are linked by hydrogen bonds forming a one-dimensional system, and for complex 8, the presence of van der Waals interactions gives a one-dimensional system, too. For complex 7, the trinuclear entities are self-assembled by azido ligands, given a hexanuclear system; each of these hexanuclear entities are self-assembled through two [Na(O)(3)(H(2)O)(3)] octahedral-sharing one-edge entities, given a one-dimensional system. The magnetic behavior of complexes 2-7 was investigated by variable-temperature magnetic susceptibility measurements. Complexes 2-6 exhibit the minimum characteristic of this kind of polymetallic species with an irregular spin state structure. The Jvalue through the oxamato bridge varied between -88 cm(-1) (for 6) and -111.2 cm(-1) (for 5). For complex 7, the values obtained were J(1) = -101.7 cm(-1) (through the oxamato ligand) and J(2) = -3.2 cm(-1) (through the azido ligand).

Journal Article↗

Climatic adaptation of Drosophila buzzatii populations in southeast Australia.

Variation in 19 traits possibly relevant for thermal adaptation was studied in 11 populations of Drosophila buzzatii collected in southeast Australia. Using stepwise multiple regression, the variation was compared to variation in geographic coordinates and to a set of climatic variables estimated for each collection site. For 13 of the traits, a significant part of the variation was explained by climatic variables and/or geographic coordinates, suggesting directional selection for adaptation to the environment in the majority of traits studied. In 10 of the traits, both geographic coordinates and climatic variables explained significant proportions of the variation, with R2 ranging from 0.075 to 0.58. Although larvae, pupae and adults of D. buzzatii share a common habitat, the measured traits were not correlated across life stages and gender. Also, there seemed to be special conditions in marginal populations near species borders, giving rise to nonlinear relations with latitude. Climate apparently does influence the adaptive evolution of the traits studied, but they also are affected by other factors that vary with latitude, longitude and distance to coast. These results highlight the complex challenges imposed by the environment on the adaptive process.

Acclimatization↗

Axial penile buckling forces vs Rigiscan radial rigidity as a function of intracavernosal pressure: why Rigiscan does not predict functional erections in individual patients.

AIM: An improved understanding of the relationship between radial and axial rigdity values would enable better appreciation of the clinical usefulness of RigiScantrade mark, the most widely utilized determination of erectile rigidity testing. Previous studies have shown that axial rigidity (measured by buckling forces) correlated well with radial rigidity (measured by RigiScantrade mark) for radial rigidity values below 60%. For radial rigidity exceeding 60%, there was poor correlation. Heretofore, there has been no physiologic explanation of this phenomenon. METHODS: During dynamic pharmacocavernosometry in 36 impotent patients, we investigated the relationship between axial buckling forces and RigiScan radial rigidity and, for the first time, how they both vary with pressure, (which we varied over over a wide functional range). In addition, we recorded multiple penile length and diameter values enabling us to relate, also for the first time, axial and radial rigidity to individual mechanical erectile tissue and penile geometric properties. RESULTS: Marked differences were found in the manner RigiScan radial rigidity units and axial buckling force magnitudes increased with increases in intracavernosal pressure values in each individual. The former asymptotically approached a maximum finite value while the latter increased continuously towards infinity. Based on data in this study, RigiScan radial rigidity values greater than 55% may be considered a necessary criteria for vaginal intromission capability in all partners but it is not a sufficient one. CONCLUSIONS: Axial and radial rigidity share a common dependency upon intracavernosal pressure, however, they are also dependent upon other unique physical determinants. For axial rigidity, additional dependent variables include cavernosal erectile tissue properties and penile geometry, while for radial rigidity, this may include tunical surface wall tension properties. Clinical devices which assess functional penile rigidity should utilize axial and not radial rigidity testing.

Equipment Design↗

Three-dimensional structure of Fab R19.9, a monoclonal murine antibody specific for the p-azobenzenearsonate group.

The crystal structure of Fab R19.9, derived from an anti-p-azobenzenearsonate monoclonal antibody, has been determined and refined to 2.8-A resolution by x-ray crystallographic techniques. Monoclonal antibody R19.9 (IgG2b kappa) shares some idiotopes with a major idiotype (CRIA) associated with A/J anti-p-azobenzenearsonate antibodies. The amino acid sequences of the variable (V) parts of the heavy (VH) and light (VL) polypeptide chains of monoclonal antibody R19.9 were determined through nucleotide sequencing of their mRNAs. The VL region is very similar to that of CRIA-positive anti-p-azobenzenearsonate antibodies as is VH, except for its third complementarity-determining region, which is three amino acids longer; it makes a loop, unique to R19.9, that protrudes into the solvent. A large number of tyrosine residues in the complementarity-determining region of VH and VL, with their side chains pointing towards the solvent, may have an important function in antigen binding.

Amino Acid Sequence↗

Hypervariability generated by natural selection in an extracellular complement-inhibiting protein of serotype M1 strains of group A Streptococcus.

In many countries, M1 strains of the human pathogenic bacterium group A Streptococcus are the most common serotype recovered from patients with invasive disease episodes. Strains of this serotype express an extracellular protein that inhibits complement [streptococcal inhibitor of complement (Sic)] and is therefore believed to be a virulence factor. Comparative sequence analysis of the 915-bp sic gene in 165 M1 organisms recovered from diverse localities and infection types identified 62 alleles. Inasmuch as multilocus enzyme electrophoresis and pulsed-field gel electrophoresis previously showed that most M1 organisms represent a distinct streptococcal clone, the extent of sic gene polymorphism was unexpected. The level of polymorphism greatly exceeds that recorded for all other genes examined in serotype M1 strains. All insertions and deletions are in frame, and virtually all nucleotide substitutions alter the amino acid sequence of the Sic protein. These molecular features indicate that structural change in Sic is mediated by natural selection. Study of 70 strains recovered from two temporally distinct epidemics of streptococcal infections in the former East Germany found little sharing of Sic variants among strains recovered in the different time periods. Taken together, the data indicate that sic is a uniquely variable gene and provide insight into a potential molecular mechanism contributing to fluctuations in streptococcal disease frequency and severity.

Antigens, Bacterial↗

Interdisciplinary teamwork and leadership: issues for psychiatrists.

OBJECTIVE: To review the constructs and applications of interdisciplinary teams in mental health services, with a particular view to ascertaining the most effective types of teams and their leadership. METHOD: Some of the most challenging questions from a psychiatrist's viewpoint regarding the functions of interdisciplinary teams in the mental health service are addressed. RESULTS: The effectiveness of the interdisciplinary team in mental health services is supported by an extensive literature that is much more qualitative and descriptive than quantitative and empirically rigorous, except as part of packages of variables subjected to randomized controlled trials. CONCLUSION: Effective interdisciplinary teamwork in mental health services involves both retaining differentiated disciplinary roles and developing shared core tasks. It requires sound leadership, effective team management, clinical supervision and explicit mechanisms for resolving role conflicts and ensuring safe practices. No one profession should hold a monopoly on leadership.

Conflict, Psychological↗

Trial of remote telemedicine support for patients with chronic respiratory failure at home through a multistation communication system.

To create and test a multistation telemedicine support system, three remote locations were connected: the homes of two patients with chronic respiratory failure, the hospital of the attending physician, and the hospital of the pulmonary specialist. Real-time connections were set up between the three locations. Medical history and biologic variables were noninvasively recorded, including blood pressure, arterial oxygen saturation, three-lead electrocardiogram, and end-tidal carbon dioxide. Both physicians shared in these data real-time. If necessary, the respiratory specialist could provide medical advice to the attending physician based on the patient's condition. The trial program resulted in the same information being exchanged remotely using the multi-station telemedicine system that would be exchanged in a direct, face-to-face encounter. This result, together with the improvement in quality of life and the establishment of appropriate treatment and cooperation between the respiratory specialist and attending physician, suggests our system can be considered useful and promising for further use.

Aged↗

Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap?

Although epileptic photosensitivity is well known, its genetics and syndromic associations are incompletely understood. Seizures triggered by photic stimulation are usually a manifestation of the idiopathic generalized epilepsies, especially juvenile myoclonic epilepsy (JME), or of the occipital epilepsies. Idiopathic photosensitive occipital epilepsy (IPOE) is a focal epilepsy with colourful elementary visual auras, often with conscious tonic head and eye version; myoclonus is not a feature. All seizures are induced by photic stimuli. We describe four families with phenotypic overlap between JME and IPOE. Families were identified if two or more affected individuals had visual auras and electro-clinical features of an idiopathic epilepsy. Family members underwent detailed electro-clinical assessment. In addition, 40 unrelated JME probands were investigated systematically for unrecognized features of IPOE (visual aura and conscious head version). There were 12 affected individuals in four families; 11 were female. Clinical onset was at 8-21 years of age. Of 10 patients with visual auras, six had conscious head version and five also experienced myoclonic jerks; eight had non-photic induced tonic-clonic seizures (TCS). Of the remaining individuals, one had myoclonic jerks and occipital spikes; the other had TCS without visual aura or myoclonic jerks. Of 10 patients with EEG studies, eight had generalized spike and wave (GSW) and six had occipital spikes. All had photosensitivity with GSW and four had additional occipital spikes. Of the 40 JME probands, six had visual aura and/or conscious head version; five of these were photosensitive. There is overlap between the clusters of clinical features used to diagnose IPOE and JME. Half of the affected individuals in our families with visual aura had myoclonic jerks; the former is characteristic of IPOE and the latter of JME. Importantly, visual aura is not regarded as part of JME, nor myoclonus part of IPOE, but our data emphasize that these symptoms may occur in both disorders. Moreover, two-thirds of individuals with visual aura had spontaneous TCS; the latter feature is not described in IPOE. Additionally, we demonstrate that visual aura and conscious head version are under-recognized features of JME, particularly among photosensitive patients. These findings could be explained by shared genetic determinants underlying IPOE and JME. Understanding the genetic basis of these disorders must account for the striking female predominance, the variable phenotypes associated with photosensitivity and the overlap of clinical features classically regarded as distinguishing focal and generalized syndromes.

Adolescent↗

Corticospinal excitability modulation to hand muscles during movement imagery.

Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were recorded from right abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles, sharing the same peripheral innervation but engaged in two different motor demands. In seven healthy and trained subjects, the latencies, amplitudes and variability of MEPs were investigated under the following, randomly intermingled, conditions: full muscular and mental relaxation; mental simulation of selective index finger or little finger abduction; mental non-motor activity (arithmetical calculation); and real motor task (little and index finger abduction). The whole procedure was performed by continuous audiovisual monitoring of electromyographic 'silence' in the tested muscles. The maximal facilitatory effects (= latency shortening and amplitude increase) on MEPs were induced by the real motor task. An amplitude potentiation of MEPs in both tested muscles was present during non-motor mental activity, in comparison to basal values. A further amplitude potentiation, without latency shifts, was confined to the muscle acting as 'prime mover' for the mentally simulated movement, according to the motor program dispatched but not executed by the subject. Similar results were also found in the F-wave, showing that mental simulation affects spinal motoneuronal excitability as well, although -- due to the lack of MEP and F-wave latency shift -- the main effect takes place at cortical level. The study shows that movement imagery can focus specific facilitation on the prime-mover muscle for the mentally simulated movement. This is mainly evident on FDI muscle, which controls fingers (i.e. the index) with highly corticalized motor representation.

Adult↗

The resolution of the Latah paradox.

Latah is a culture-bound syndrome from Malaysia and Indonesia. Persons exhibiting the Latah syndrome respond to minimal stimuli with exaggerated startles, often exclaimning normally inhibited sexually denotative words. Sometimes Latahs after being startled obey the commands or imitate the actions of persons about them. Most episodes of Latah are intentionally provoked for the amusement of onlookers. Similar sets of interactive behaviors have been reported from genetically and culturally unrelated populations (e.g., Bantu, Ainu, and French Canadians). Since competent anthropological investigators have shown Latah to be intimately tied to specific factors in the cultural systems of the Southeast Asian societies in which it is found, its occurrence elswhere has been considered paradoxical. New data, including films and videotapes of hyperstartling persons from Malaysia, the Philippines, Japan, and the United States, suggest a model capable of resolving the apparent paradox by showing how the various forms of latah are culture-specific exploitations of a neurophysiological potential shared by humans and other mammals. Latah provides an especially revealing example of the complex ways in which neurophysiological, experiential, and cultural variables interact to produce a strongly marked and phenomenon.

Arousal↗

Measuring nursing governance.

BACKGROUND: Despite outcomes studies measuring such variables as job satisfaction, autonomy, professionalism, turnover, leadership styles, and more recently, cost-effectiveness, no consistent relationships have been established between shared governance models and outcomes. OBJECTIVES: To define and develop an instrument to measure the governance of hospital-based nurses. METHODS: The 88-item Index of Professional Nursing Governance (IPNG) was developed to measure professional nursing governance of hospital-based nurses. Psychometric properties were tested with 1,162 registered nurses from 10 hospitals. RESULTS: Content validity after item generation was .95, using Popham's average congruency procedure. Six factors explained 42% of the variance with subscale intercorrelations between .43 and .67. All subscales had a high degree of internal consistency (alphas .87 to .91); test-retest reliability was .77. Construct validity testing showed that scores between shared governance and traditionally governed hospitals were significantly different. A correlation was found between scores on the IPNG and the Hague and Aiken Index of Centralization. CONCLUSIONS: The results of this study support the validity of the 88-item IPNG as a reliable instrument for measuring the distribution of professional nursing governance of hospitals.

Adult↗