Multiple personality in eating disorder patients.

Although the overlap between childhood sexual and physical abuse and eating disorders is well known, little work has been done on the sequelae of childhood trauma in eating disorder patients. Dissociative phenomena are common in adult survivors of childhood abuse, with multiple personality disorder (MPD) being the most extreme form of dissociative disorder. We describe two women who presented for inpatient treatment of eating disorders who were subsequently found to have MPD. Because the eating pathology in these patients contained atypical features related to the MPD process, uncovering MPD was critical in the treatment of their eating behavior. MPD should be considered in any atypical or treatment-resistant eating disorder patient.

Pharmacotherapy of social phobia: an interim report of a placebo-controlled comparison of phenelzine and atenolol.

Forty-one patients meeting DSM-III criteria for social phobia completed a randomized comparative trial of the monoamine oxidase inhibitor phenelzine, the cardioselective beta-adrenergic blocker atenolol, and placebo. No significant differences were seen after 4 weeks of treatment in this preliminary trial. At the end of 8 weeks, however, phenelzine demonstrated greater efficacy than atenolol or placebo on dimensional ratings of overall severity of social phobia. No atenolol-placebo differences were observed. The authors shall present maintenance and discontinuation findings in a final report. Phenelzine may act in patients with social phobia by directly reducing interpersonal hypersensitivity.

Drug treatment of phobias. Efficacy and optimum use.

In the last decade anxiety disorders have been the focus of intensive research in the psychiatric community, resulting in a rapid growth in our understanding of these illnesses. Diagnostic, biological, and psychopharmacological investigations have revealed important distinctions among these disorders which enable the clinician to make well-informed therapeutic choices and frequently ameliorate or even eliminate anxiety symptoms and related phobic behaviour. The principles of treatment can be simply stated: 1. Careful diagnostic evaluation through history and exclusion of medical and psychiatric conditions which mimic anxiety disorders. 2. Treatment selection based on diagnosis and formulation with the patient of the goals and expected outcome of pharmacotherapy. 3. Systematic application of each drug treatment in sufficient dosage and for an adequate duration permitting progression to the next agent when results are not optimal. 4. Addition of non-pharmacological interventions, usually behavioural therapy, to decrease phobic behaviour. 5. Development of a maintenance or discontinuation strategy tailored to the needs of the patient.

Pituitary adrenocortical unresponsiveness in lactate-induced panic.

The hypothalamic-pituitary adrenal (HPA) axis responds to a variety of physical and emotional stimuli with increased output of adrenocorticotropic hormone (ACTH) and cortisol, yet there is little known about the activity of this system during episodes of severe anxiety in patients with DSM-III-defined anxiety disorders. To explore further whether alterations of the HPA axis occur during various anxiety states, we measured ACTH and cortisol during lactate infusion in patients with panic disorder and agoraphobia. In eight patients who panicked during lactate infusion, there were no elevations in either ACTH or cortisol. Further, the patterns of hormone secretion did not differ among patients who panicked, nonpanicking patients, or controls. This negative result suggests that the neurobiological mechanisms that mediate panic differ from those responsible for other fear responses.

Properties of the imidazolylacetolphosphate aminotransferase produced in a mutant demonstrating no apparent genetic involvement of the structural gene.

Genetic studies with strain hisBH22 of Salmonella typhimurium indicate it contains a deletion within the histidine operon involving part of the hisH gene and all of the hisB gene, but not extending into the adjacent hisC gene which is adjacent to hisB. However, the specific activity of the hisC product, imidazolylacetolphosphate aminotransferase (EC 2.6.1.9), in this strain is only 10 to 15% of that found in extracts from other mutants with a normal hisC gene. We have examined the rate of aminotransferase synthesis in this mutant and we find that the rate of synthesis of aminotransferase activity is low in mutant hisBH22, but the rate increases as the temperature of growth is lowered from 37 to 23 C. The low rate of enzyme accumulation is not due to holoenzyme instability at 37 C but instead is due to apoenzyme instability at this temperature. By transducing the hisBH22 marker into a pyridoxine auxotroph and derepressing the histidine operon under conditions where the intracellular concentration of pyridoxal phosphate would be expected to be low, we were able to demonstrate significant apoenzyme production only at the lower temperature. We suggest that the explanation for low aminotransferase specific activity at 37 C is due to the presence of reduced numbers of catalytically active units caused by normal production of an unstable mutant apoenzyme with only approximately 15% of the molecules being activated to holoenzyme. The holoenzyme from strain hisBH22 is stable during growth of this strain at 37 C.

In vivo and in vitro complementation between guaB and in vivo complementation between guaA auxotrophs of Salmonella typhimurium.

guaA and guaB mutants of Salmonella typhimurium were isolated utilizing the mutagen, nitrous acid. The guaB mutants were defective for inosine 5'-monophosphate (IMP) dehydrogenase activity and those mutants classified as guaA exhibited no xanthosine 5'-monophosphate aminase activity. In vivo complementation maps were determined for the mutants. The guaB map indicated that at least three complementation regions existed whereas five complementation regions were observed for the guaA mutants. The demonstration of in vitro complementation was also achieved for the guaB mutants by utilizing a process of denaturation and renaturation. All of the guaB mutants that exhibited in vivo complementation were found to exhibit in vitro complementation. No correlation was found between the degree of in vivo complementation exhibited by the various pairs of mutants and the specific enzyme activities of the same mutant pair that yielded in vitro complementation. The kinetic parameters for three of the most active guaB "complemented" enzymes and a renatured wild-type IMP dehydrogenase were then examined. No apparent differences were found in the K(m) values between any of the enzymes for substrate, IMP, activator ion, K(+), and coenzyme, oxidized nicotinamide adenine dinucleotide. Some differences were noted in the apparent V(max) values; the best "complemented" enzyme yielded only 20% of the velocity exhibited by renatured wild-type enzyme.

Aminotransferase from a deletion mutant in the histidine operon.

The imidazolylacetolphosphate:l-glutamate aminotransferase from the deletion mutant hisHB22 has been partially characterized. Although genetic studies have not yet shown the deletion to involve the structural information for this enzyme, physical studies indicate that an abnormal enzyme is produced. Evidence is presented which, together with previous data on the characterization of the enzyme, indicates that the catalytic integrity of the enzyme is intact, and that the low specific activity seen in cell extracts is due to formation of an enzyme which has a reduced coenzyme content. It is suggested that this reduced coenzyme content is due primarily to a reduced affinity of the enzyme (nascent or apo-) for its coenzyme, and that the coenzyme must be incorporated into the enzyme at the moment of synthesis for formation of a functional protein.