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We have used hydroxy-radical and deoxyribonuclease-I footprinting to probe the interaction of mithramycin with DNA fragments containing the sequences (AT)10X(AT)10 (X = CCCG, CCGC or CGGC) and A14GCCCT15. As expected the drug produces clear footprints located around the central four GC base pairs. The exact position of the footprint is different for the four sequences; the footprint with CCCG is displayed by two base pairs in the 5' direction relative to GCCC. These variations are explained by suggesting that mithramycin avoids the dinucleotide CG and binds better to GG/CC than GC. Although there is little change in deoxyribonuclease-I cleavage of the surrounding blocks of (AT)n, cleavage by deoxyribonuclease II is markedly enhanced and certain thymines on the 5' side of the ligand-binding site become hyperreactive to hydroxy-radical attack. Adjacent regions of An.Tn show enhanced rates of deoxyribonuclease-I cleavage in the presence of the antibiotic.

We have studied the binding of echinomycin to DNA fragments containing GC-rich regions flanked by blocks of alternating AT by DNase I footprinting and diethylpyrocarbonate modification. Regions of alternating AT flanking the sequences CCCG, CCGC, CGGC and GG show a four base pair DNase I cleavage pattern and reaction of alternate adenines with diethylpyrocarbonate. This pattern is strongest when the AT-block is immediately adjacent to the CpG ligand binding site. We explain these phenomena by suggesting that echinomycin binds to the dinucleotide step ApT in a cooperative fashion. The cooperative effects can be transmitted through the dinucleotide step GC but not CC or AA. No such repetitive patterns are seen with surrounding regions of (ATT).(AAT). Evidence is presented for secondary drug binding sites at CpC and TpG with weaker interaction at the CpG site within the hexanucleotide TTCGAA.

We report a successfully treated case of severe thallium intoxication that required 95 days of assisted ventilation and 224 days of hospitalization. Monitoring of the patient for 500 days by measuring thallium in whole blood, serum, and urine is documented, and the role of the laboratory and utility of the measurements are considered.

This study of psychiatric illness among 4098 patients attending 91 general practitioners compares 2 methods of case identification: 'conspicuous morbidity' by the doctor's own assessments, and 'probable prevalence' by the patients' responses to the General Health Questionnaire (GHQ). In general, the latter gives somewhat higher estimates than the former, but there are wide variations in morbidity between practices. The ability of each general practitioner to detect psychiatric illness was measured by computing Spearman's correlation coefficient between his assessments and the GHQ scores of his patients. The mean correlation coefficient was + 0.36, but the range was very wide (0.09-0.60). The first part of the study deals with various demographic characteristics of the patients themselves which are associated with an increased likelihood of the doctor detecting a psychiatric illness; such factors include unemployment, female sex, and marriages which have ended by separation, divorce or death. The second part of the study examines characteristics of the doctors themselves in an attempt to account for the wide variation between them in their ability to detect psychiatric illness. A research psychiatrist made detailed observations on 2098 interviews carried out by 55 general practitioners. Each doctor's verbal and non-verbal styles were recorded minutely, and in addition various global ratings were made. The doctors completed personality inventories and supplied details of training and professional background. It was possible to account for 67% of the variance of correlation coefficient mainly in terms of 2 dimensions: 'interest and concern' and 'conservatism'. The way in which the doctor interviews his patients is shown to be important, but there are interactions between interview style and the doctor's personality.

A group training course utilizing videotaped material and discussion proved to be as effective as traditional methods in teaching medical students to obtain information from co-operative psychiatric patients. There were also some clear indications that group video training may prove valuable in teaching specific interview techniques, although its full potential in this area has yet to be explored.