Sequence effects on local DNA topology.

Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1' protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1' distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 A depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is greater than 4.5 A. In GA steps, x varies within rather wide limits in the range 3.8-4.5 A, whereas in AA steps the lower limit is 3.7 A and the upper limit is approximately 4.2 A. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5' end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3' end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3' end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B' structure when the substitution produces an AnTm tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1' distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1' distances depending on the DNA sequence. By using high-resolution x-ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1'-H1'. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs.     

Correlates of hopelessness in psychiatrically hospitalized children

The importance of hopelessness within the study of childhood psychiatric disorders is becoming increasingly apparent. The present study divides a child inpatient sample (age 7 to 12 years) into two groups based on scores from the Kazdin Hopelessness Scale for Children. Comparisons made between the two groups on various measures showed that children with high hopelessness had lower cognitive ability, "difficult child" temperament characteristics, more anxiety, lower self-esteem, and a higher degree of psychopathology than the low-hopelessness group. The role of hopelessness in academic success and future psychopathology are discussed.     

The impact of different coding systems on DRG assignment and data

The Diagnosis Related Group (DRG) classification system is widely used to describe the casemix of acute care hospitals, making it possible to compare the casemix of hospitals from different countries. However, in order to fully understand these comparisons, it is necessary to clarify the impact which the different coding systems used in various countries may have had on the results. The DRG system is based on codes from the International Classification of Diseases 9th Revision Clinical Modification (ICD9CM). Countries which use other coding systems convert, i.e. map, their codes into the nearest ICD9CM equivalent before allocating the DRGs. The impact of mapping on both medical and surgical DRGs is discussed and new titles are given for the affected DRGs. As far as possible, problems caused by mapping are distinguished from those caused by differences in coding practices. Based on the analysis of the classification systems, the mapping tables and the resulting DRG data, it is concluded that using mapped data does not have a great impact on the DRGs. Only 37 DRGs (7.8%), 15 medical and 22 surgical classes, are affected by mapping problems. However, while the scale of these problems is not large, given the large number of different surgical classification systems currently in use in Europe, the introduction of a standard surgical classification system for Europe is recommended.     

Risk of intracranial aneurysm surgery in the good grade patient: early versus late operation

To evaluate the risk of definitive intracranial microsurgical aneurysm obliteration as a function of the timing of the operative intervention, we retrospectively reviewed 106 consecutive patients in good clinical condition who underwent such surgery. The patients who were operated upon within the first 8 days of their most recent subarachnoid hemorrhage formed the "early" group; the patients operated upon between the 9th and 31st day were considered to have undergone "late" surgery. On the basis of their clinical outcome the patients were allocated to one of four outcome categories ("good," "fair," "death") both at the time of their hospital discharge and at their most recent clinical re-evaluation, a minimum of 6 months after discharge from the hospital. There was no significant difference in the operative mortality in each group (early surgery, 5%; late surgery, 4%); additionally, no significant difference was noted in the incidence of either intraoperative complications or postoperative morbidity. A suggestive but statistically insignificant increase in the incidence of postoperative cerebral ischemic events was seen in the "early" surgery group (8% vs. 4% for the "late" surgery group). The potential significance of these findings for the timing of intracranial aneurysm surgery is discussed.     

The cardiovascular effects of bromocriptine in Parkinsonism

1 The cardiovascular effects of bromocriptine, a dopamine receptor agonist, were investigated in twenty-eight Parkinsonian patients.

2 Bromocriptine caused a significant impairment of postural compensation with a fall in systolic pressure and an absence of the rise in diastolic pressure after standing for 1 min when patients taking active drug were compared to the same patients on placebo. The hypotensive effect persisted for at least 6 weeks of treatment. There was also a significant reduction in supine heart rate.

3 One patient had marked falls in supine and erect blood pressure after a single oral dose of bromocriptine (2.5 mg) and a further patient developed paroxysmal atrial tachyarrhythmias. Both blood pressure and heart rate changes reversed spontaneously after stopping bromocriptine.

4 It is proposed that dopaminergic mechanisms either in the central nervous system or the periphery contribute to cardiovascular regulation in man.

     

Evidence for anomalous lateralization across domain in ADHD children as well as adults identified with the Wender Utah rating scale

Two studies assessed the relation between ADHD symptomatology and correlates of cerebral dominance. In the first, laterality was examined in school children (N=57), 28 with ADHD. Parental reports of greater attentional symptoms were related to non-righthandedness, but teacher reports were related to anomalous laterality of foot, ear and eye, as well as hand. This suggests that the previously reported association between ADHD and non-righthandedness may not be unique, but instead indicative of a more general condition of anomalous lateralization. This possibility was examined in study two, in which 234 undergraduates were assessed. As expected, the 26 adults identified by the Wender Utah Rating Scale (WURS) as retrospectively reporting more ADHD characteristics were found to be generally male. Also, in a replication of study one, enhanced WURS scores were associated with anomalous lateralization beyond handedness. In this case, ADHD characteristics were associated with a shift away from a right bias for hand, foot, and ear, but not eye. Factor analysis of the extensive Steenhuis and Bryden handedness questionnaire was then undertaken to determine whether all aspects of handedness, or only a subset, are associated with ADHD. The factor analysis indicated that the retrospective reports of ADHD characteristics were associated with only two of the three dimensions. Though limitations such as the gender composition of the groups in study one tempers the conclusions, the results of both studies support previous findings that ADHD is associated with anomalous laterality, but also indicate that non-righthandedness is not an adequate characterization of this relationship.     

Ischemic heart disease in black South African stroke patients

BACKGROUND AND PURPOSE: Stroke patients in western countries frequently have coronary artery disease (CAD). In black Africans, CAD has been reported as being rare in both stroke patients and the general population. In this study, an attempt has been made to determine the prevalence of CAD in a black South African stroke population. METHODS: The prevalence of CAD was determined by indicators identified through a series of 5 observational studies in black patients diagnosed with stroke. CAD indicators included (1) bedside diagnosis in 741 patients; (2) resting ECG in 555 consecutively admitted patients; (3) a combination of clinical examination, cardiac ultrasound, radionuclide scintigraphy, and multigated blood pool studies in 102 consecutively admitted patients; (4) thallium scintigraphy in 60 patients; and (5) necropsy in 23 patients. RESULTS: On bedside questioning, only 0.7% complained of previous angina. There was no history given of myocardial infarction (MI), but documentation of this was found in the clinical notes of 0.7% of the patients. In the resting ECG study, evidence of myocardial ischemia was present in 14.6% and MI in 2.1%. In the combined study, cardiac ischemia was documented on ECG in 12.7% of patients and evidence of previous MI in 5.8%. Cardiac scintigraphic studies revealed changes of myocardial ischemia in 31.7% and MI in 13.3% of the 60 patients studied. Four (17.4%) of 23 patients in the necropsy study had histological evidence of previous MI, and 50% of all patients had evidence of >50% atherosclerotic stenosis in 1, 2, or 3 coronary arteries. CONCLUSIONS: The prevalence of CAD in black African stroke patients is significantly higher than has been documented in the general nonstroke black population as well as in stroke patients. Black stroke patients may have a risk for CAD similar to that of their white counterparts.     

A controlled trial of an educational pamphlet to prevent disability after occupational low back injury

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury. BACKGROUND: Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues. METHODS: A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews. RESULTS: Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly. CONCLUSIONS: In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.     

The European Donor Hospital Education Programme (EDHEP): enhancing communication skills with bereaved relatives

Intensive care medical and nursing staff self-rate their communication skills as improved following attendance at the European Donor Hospital Education Programme (EDHEP) workshop. A prospective study was conducted to determine what impact EDHEP has on communication skills. Doctor-nurse pairs from 10 experimental and 10 control Intensive Care Units undertook two standardized simulated relative encounters (Breaking Bad News and Donation Request) at three measurement points (pre, post and follow-up). Nurses showed no change in communication skills. Experimental group doctors showed significant improvement in breaking bad news and requesting donation; most of these improvements were not maintained. Control group doctors showed some improvement in breaking bad news, indicating that participating in measurement by itself initiates some transient change in communication skills. Attendance at EDHEP does lead to significant improvement in some, but not all, communication skills essential in breaking bad news and requesting donation. Further research is necessary to determine what factors additional to EDHEP will contribute to enduring change in these particular skills.     

Inhibition of uropathogenic biofilm growth on silicone rubber in human urine by lactobacilli – a teleologic approach

The ability of three Lactobacillus strains to inhibit the adhesion and growth of naturally occurring uropathogens on silicone rubber was investigated in human urine. The importance of biosurfactant production by Lactobacillus in discouraging uropathogen growth was determined in relation to the binding affinities of the lactobacilli for silicone rubber. L. fermentum B54 markedly inhibited uropathogen growth on the silicone rubber disks after 8 days for all five men included in the study, albeit to various extents ranging from 77% to 100%. In urine from women, however, this inhibition was less clear, as it was absent for two of the four women participating in this study. L. casei rhamnosus 36 completely discouraged uropathogen growth on the disks after 8 days for three of the four women, whereas its effect in urine from men was less pronounced (inhibition ranged from 48% to 100% and was absent for one man). L. casei rhamnosus ATCC 7469^T was the least inhibitory Lactobacillus strain tested and inhibition was absent for a number of both male and female participants, possibly as a result of the low binding affinity of this strain for silicone rubber and of its inability to release biosurfactants. We conclude that the inhibition of uropathogen growth is dependent on the Lactobacillus strain involved, and for L. fermentum B54 it was demonstrated to be sex-related. Hence, inhibition must be considered a multifactorial process.