Systematic counselling by general practitioners for promoting physical activity in elderly patients: a feasibility study.

RESEARCH QUESTIONS: To investigate how the daily physical activities of elderly patients can be enhanced by systematic counselling conducted by general practitioners (GPs). METHODS: In this feasibility study with pre-post design, 29 people (14 females, mean age 72.2 years, SD = 6.1) were enrolled during routine visits by two general practitioners. A baseline assessment of current physical activity based on the stages according to the Transtheoretical Model was followed by a counselling session. The target behaviour was defined by performance of 30 minutes of daily moderate-intensity activities that increase the breathing rate, on five days per week. At the 2-month follow-up, subjects were assessed for improvement in stage of physical activity since baseline. After the end of the intervention, participating GPs and patients were asked questions focusing on the feasibility, acceptance and usefulness of counselling. RESULTS: Interview results showed that the two GPs considered the counselling protocol easy to handle and useful for promoting physical activity. Counselling sessions were especially encouraging for the not sufficiently active people. Most of them would like to have additional counselling session. At baseline, 9 of 29 people were sufficiently active. After 2 months, this proportion was 21 of 29. The mean of the number of minutes of physical activity during the previous 4 weeks increased from 247 to 436 minutes (weekly). CONCLUSIONS: The programme was judged positively by the general practitioners and the participating elderly patients. Systematic counselling by general practitioners led to an increase in the physical activity behaviour. Therefore, a more rigorous randomised controlled trial with adequate followup is recommended.

Monofunctional adenine N-3 adducts of melphalan: occurrence at a mutational hotspot sequence and resistance to removal by AlkA protein.

Previous work showed that a CTAAA sequence in the supF gene of the shuttle plasmid pZ189 was a hotspot for mutagenesis by the aromatic nitrogen mustards melphalan and chlorambucil, and indirect evidence suggested adenine N-3 adducts as premutagenic lesions. In order to characterize the adducts formed at this sequence more directly, a substrate was prepared in which the three adjacent adenines in the CTAAA sequence were 3H-labeled. Following treatment of this substrate with [14C]melphalan, thermolabile adducts were depurinated and analyzed by HPLC. Only a single peak bearing both 3H and 14C label was detected and it coeluted with the single major adduct formed by the reaction of melphalan with free adenine base. Various spectrometric analyses of this species were all consistent with its identification as a monofunctional adenine N-3 adduct of melphalan. There was no evidence for any bifunctional adducts involving the labeled adenines. There was little if any release of the adenine N-3 adduct of melphalan by Escherichia coli AlkA protein, under conditions where 3-methyladenine was quantitatively released. The results support the proposal that monofunctional adenine N-3 adducts are intermediates in the generation of A.T-->T.A and A.T-->C.G transversions by aromatic nitrogen mustards.

Post-traumatic stress disorder among Special Forces Vietnam veterans.

Fifty-seven Special Forces Vietnam Veterans were studied to determine if special selection and rigorous training affected the frequency and pattern of predictors of post-traumatic stress disorder (PTSD). No absolute immunity to PTSD was conferred. Frequency (25%) and predictors of PTSD were similar to those reported for other groups of Vietnam Veterans. Symptoms of PTSD were associated with poorer pre-service relationships, being wounded, being wounded after return from R&R, having friends missing in action, feeling guilt over the death of a friend, lack of emotional preparation to leave the unit or service, and failure to discuss feelings upon return from Vietnam.

Verbalized anger and accusatory "you" messages as cues for anger and antagonism among adolescents.

This study investigated the impact of communications of negative feelings between adolescents in close relationships. High school boys and girls were asked to imagine discussing a relationship problem with a personally close partner and to rate likely reactions to four kinds of statements: assertively expressed distress, assertively expressed anger, aggressively expressed distress, and aggressively expressed anger. Accusatory "you" statements were rated as more aversive and evoked stronger antagonistic response inclinations than assertive "I" statements. Statements depicting anger were rated as more aversive and evoked stronger antagonistic response inclinations than statements depicting distress. Results were similar for boys and girls. Implications of the findings and directions for further research are discussed.

Trained motor imitation by bottlenose dolphins (Tursiops truncatus).

Each of two bottlenose dolphins, Tursiops truncatus, was trained to mimic a set of behaviors on command. They were tested on transfer of the mimic command to a set of familiar behaviors which they had not previously been commended to mimic. They were similarly tested on two novel behaviors. One dolphin demonstrated complete mimicry of 5 of 11 familiar behaviors; the other dolphin mimicked 1 of 9 behaviors. None of the mimicked behaviors was exhibited to an inappropriate model, suggesting that performance was not due to chance. Neither dolphin imitated the novel behaviors.

Specificity and kinetics of interstrand and intrastrand bifunctional alkylation by nitrogen mustards at a G-G-C sequence.

Previous work showed that melphalan-induced mutations in the aprt gene of CHO cells are primarily transversions and occur preferentially at G-G-C sequences, which are potential sites for various bifunctional alkylations involving guanine N-7. To identify the DNA lesion(s) which may be responsible for these mutations, an end-labeled DNA duplex containing a frequent site of melphalan-induced mutation in the aprt gene was treated with melphalan, mechlorethamine or phosphoramide mustard. The sequence specificity and kinetics of formation of both interstrand and intrastrand crosslinks were determined. All mustards selectively formed two base-staggered interstrand crosslinks between the 5'G and the G opposite C in the 5'G-G-C sequence. Secondary alkylation was much slower for melphalan than for the other mustards and the resulting crosslink was more stable. Mechlorethamine and phosphoramide mustard induced intrastrand crosslinks between the two contiguous Gs in the G-G-C sequence in double-stranded DNA, but melphalan did not. Molecular dynamic simulations provided a structural explanation for this difference, in that the monofunctionally bound intermediates of mechlorethamine and phosphoramide mustard assumed thermodynamically stable conformations with the second arm in a position appropriate for intrastrand crosslink formation, while the corresponding melphalan monoadduct did not.

Selectivity in the responses of hamsters to conspecific vocalizations.

Lordosis responses by estrous hamsters were triggered by brief manual stimulation. Lordosis durations then were timed, as manual stimulation was discontinued, and subjects were exposed to tape-recordings of conspecific vocalizations reproduced at intensities of 0-60 dB SPL. Relative to the durations observed in the presence of ambient noise alone, recordings of stress-elicited screams failed to facilitate lordosis regardless of stimulus intensity. In contrast, ultrasounds by male or female hamsters did prolong lordosis, and to extents that were directly related to intensity but unrelated to the sex of the caller. The very different responses to screams and ultrasounds suggest that the ability to facilitate sexual behavior is at least somewhat specific to ultrasounds and is not shared by all vocalizations reflecting states of high general arousal. On the other hand, the similar responses elicited by male and female ultrasounds suggest that these calls convey similar messages and that structural differences between them effect changes in call localizability, not meaning.

DNA damage induced by bleomycin, neocarzinostatin, and melphalan in a precisely positioned nucleosome. Asymmetry in protection at the periphery of nucleosome-bound DNA.

The antitumor drugs bleomycin, neocarzinostatin, and melphalan all damage DNA by mechanisms which involve binding in the minor groove. In order to examine at high resolution the modulating effects of chromatin structure on the action of these drugs, an end-labeled DNA fragment from the Xenopus laevis 5 S rRNA gene was reconstituted with histone octamers to form a precisely positioned nucleosome. For each drug, DNA damage at specific sequence positions in the fragment was then compared for nucleosome-bound versus naked DNA. Reconstitution into nucleosomes resulted in a marked inhibition of the DNA cleavage induced by bleomycin (5-fold) and neocarzinostatin (2.4-fold) in the central region of nucleosomal DNA. However, at the periphery of nucleosome-bound DNA, a distinct asymmetry was apparent, with marked inhibition of cleavage toward the upstream side, but little if any inhibition toward the downstream side, which overlaps the binding site of the transcription factor TFIIIA. In the case of melphalan, alkylation at adenine N-3 was inhibited by nearly 2-fold throughout the nucleosome, whereas alkylation at guanine N-7 was either slightly inhibited or slightly enhanced, depending on sequence position. None of the drugs showed the 10-base pair periodicity characteristic of hydroxyl radical-induced cleavage of nucleosomal DNA. The results are consistent with a model in which minor groove sites in nucleosome-bound DNA remain relatively accessible to small molecules, even where the minor groove faces the histone core, and in which drug-induced DNA damage is inhibited by conformational constraints imposed on DNA by nucleosome structure. Furthermore, the degree of such constraints appears to be sequence-dependent, at least near the periphery of nucleosome-bound DNA.

Thermolabile adenine adducts and A.T base pair substitutions induced by nitrogen mustard analogues in an SV40-based shuttle plasmid.

It was previously shown that the predominant mutations induced by melphalan (L-phenylalanine mustard) in the supF gene of shuttle plasmid pZ189 during replication in human cells are A.T----T.A transversions. In order to determine whether adenine adducts were formed at sequence positions corresponding to these mutations, melphalan-induced thermolabile adducts were mapped in the supF gene by selective depurination followed by strand cleavage in alkali. All A.T base pairs which were frequent sites for melphalan-induced A.T----T.A transversions were also prominent sites for formation of thermolabile adenine adducts. Although no mutations were detected at some prominent adduct sites, there was a significant correlation between adduct sites and mutation sites. While runs of two or more adenines were particularly prominent adduct sites, comparison of results obtained with 3'- and 5'-end-labeled DNA gave no evidence for intrastrand cross-links between adjacent adenines. Chlorambucil, another aromatic nitrogen mustard, showed sequence specificities for both mutagenesis and adenine adduct formation nearly identical to those seen with melphalan. The nonaromatic analogues mechlorethamine and phosphoramide mustard were much less efficient in inducing thermolabile adenine adducts, and mechlorethamine induced significantly fewer transversions at A.T base pairs than chlorambucil or melphalan. Formation of thermolabile adenine adducts by the aromatic nitrogen mustards was markedly reduced by blockage of the minor groove with distamycin, or by prior heat denaturation of the DNA. These results suggest that alkylation occurs primarily at the N-3 rather than N-7 position of adenine, probably as a consequence of the affinity of the aromatic rings of melphalan and chlorambucil for the minor groove.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of distamycin on chlorambucil-induced mutagenesis in pZ189: evidence of a role for minor groove alkylation at adenine N-3.

Previous work has shown that the bifunctional alkylating agent chlorambucil induces thermolabile adenine adducts and that the predominant chlorambucil-induced mutations in shuttle vector pZ189 are transversions at AT base pairs. In order to assess the role of thermolabile adducts in generating these transversions, pZ189 was treated with chlorambucil in the presence of distamycin, which specifically blocks formation of thermolabile adenine adducts. Analysis of the mutations resulting from replication of the damaged vector in human 293 cells showed that base substitutions at AT base pairs were specifically suppressed in concert with suppression of thermolabile adducts at specific sites in the supF target gene, strongly supporting a role for these adducts in mutagenesis. Since there is considerable evidence that these adducts are N-3 alkylations, a computer graphics model of such an adduct was constructed. Modeling studies indicated that the adduct could be formed with little distortion of the DNA helix. Analysis of the adduct using the HINT (Hydropathic INTeractions) program was consistent with the proposal that favorable hydrophobic interactions of the phenyl ring of chlorambucil with the wall of the minor groove may promote adenine N-3 alkylation by this drug.

The Honolulu posttraumatic stress disorder stimulus set.

We present word and picture stimuli constituting a validated stimulus set appropriate for cognitive investigations of posttraumatic stress disorder (PTSD). Combat related and neutral words and pictures were rated by Vietnam veterans with PTSD and by three comparison groups along four dimensions: unpleasantness, Vietnam relevance, stressfulness, and memorability. There were distinctive patterns of responses by the PTSD group which efficiently discriminated the individuals in this group from those in the control groups. These stimuli have the potential to be developed as a diagnostic instrument.

Compelled attention: the effects of viewing trauma-related stimuli on concurrent task performance in posttraumatic stress disorder.

We examined the ability of Vietnam veterans with PTSD to focus attention on a primary digit detection task while concurrently viewing neutral or Vietnam-related picture and word distractors. Controlling for combat exposure, military service, and psychopathology, veterans with PTSD took longer to detect the target when Vietnam-related pictures were distractors. There were no reaction time differences when word stimuli were distractors. The latency effect was specific to trials with trauma-related pictures and did not spread to neutral trials interleaved within a mixed block of trauma and neutral pictures. Individuals with PTSD recalled proportionally more Vietnam-related words than other groups, implying differential attention to Vietnam-related words. Attending to trauma-related pictures interferes with performance of a concurrent task by individuals with PTSD.