Odor differences between enantiomeric isomers.

The enantiomers of R- and S-carvone, R- and S-carvotanacetone, R- and S-trans-dihydrocarvone, and R- and S-cis-dihydrocarvone were synthesized from R- and S-carvone, and all were subjected to gas-liquid chromatographic purification. Sensory analysis of the highly purified compounds revealed odor differences between enantiomeric pairs.

An evaluation of family therapy in anorexia nervosa and bulimia nervosa.

A controlled trial comparing family therapy with individual supportive therapy in anorexia nervosa and bulimia nervosa was undertaken. Eighty patients (57 with anorexia nervosa; 23 with bulimia nervosa) were first admitted to a specialized unit to restore their weight to normal. Before discharge, they were randomly allocated to family therapy or the control treatment (individual supportive therapy). After one year of psychological treatment, they were reassessed, using body weight, menstrual function, and ratings on the Morgan and Russell scales. Family therapy was found to be more effective than individual therapy in patients whose illness was not chronic and had begun before the age of 19 years. A more tentative finding was the greater value of individual supportive therapy in older patients. To our knowledge, this is the first controlled trial of family therapy in anorexia nervosa and clarifies the specific indications for this treatment.

Family and individual therapy in anorexia nervosa. A 5-year follow-up.

BACKGROUND: There is evidence that specific psychological treatments are effective in patients with eating disorders. Our goal was to determine by means of a controlled trial whether psychological treatments, previously found to be effective in anorexia nervosa, gave rise to enduring benefits. METHODS: A 5-year follow-up was conducted on patients who had participated in a previous trial of family therapy for anorexia and bulimia nervosa. Family therapy or individual supportive therapy had been administered to 80 outpatients for 1 year beginning on discharge from hospital after weight restoration. The 80 patients had been subdivided into 4 prognostically homogeneous groups of which 2 turned out to be the most important: patients with early onset and short history of anorexia nervosa, and patients with late-onset anorexia nervosa. At the 5-year follow-up, the efficacy of the outpatient therapies was again assessed by the maintenance of weight, and the categories of general outcome and dimensions of clinical functioning defined by the Morgan-Russell scales. RESULTS: Significant improvements were found in the group of 80 patients as a whole, mainly attributable to the natural outcome of anorexia nervosa, and most evident in the early onset and short history group, as expected. Within 2 of the prognostic groups, significant benefits attributable to previous psychological treatments were still evident, favoring family therapy for patients with early onset and short history of anorexia nervosa and favoring individual supportive therapy for patients with late-onset anorexia nervosa. CONCLUSIONS: Much of the improvements found at a 5-year follow-up can be attributed to the natural outcome of the illness. Nevertheless, it was still possible to detect long-term benefits of psychological therapies completed 5 years previously.

The clinical relevance of salivary amylase monitoring in bulimia nervosa.

The aim of this study was to evaluate the clinical relevance of amylase level monitoring as an objective measure in diagnosis and assessment of treatment response in bulimia nervosa. Thirty-three subjects who fulfilled DSM-111-R criteria for bulimia nervosa had serum levels of total and salivary amylase monitored during an 8-week treatment trial. At the beginning of treatment, the average total amylase level was within the upper limits of normal, whereas average salivary amylase levels were abnormally high. During the course of treatment, there was a significant reduction in the average salivary isoenzyme to within the normal range. Significant reductions in amylase levels were recorded in patients with good treatment outcome, but not in those with poor outcome. Amylase levels were not significantly correlated with severity of bulimic symptoms. These results do not justify the use of amylase assays as a routine diagnostic or monitoring test, but isoenzyme monitoring may provide useful clinical information in selected cases.

Anorexia nervosa and the adrenal: the effect of weight gain.

Cortisol (F) and dehydroepiandrosterone (DHA) were measured following each 5 kg gain in weight in a group of 16 patients with anorexia nervosa admitted to hospital for refeeding. The mean percentage of standard weight on admission was 65% and that on discharge was 92%. Basal plasma cortisol fell gradually throughout the inpatient period, the correlation coefficient of the regression line relating percentage of standard weight to plasma cortisol in all patients was -0.559 (p less than 0.001). Adrenal androgen production, however, increased with weight gain and the correlation coefficient of the regression line of androgen production against percentage of standard weight was +0.303 (p less than 0.01). The DHA/F ratio increased with weight gain. This suggests that weight gain in the patient with anorexia nervosa could be associated with increased activity in the adrenal 17,20-lyase enzymes and a decrease in the activity of the 3-beta hydroxysteroid dehydrogenase. The possibility that these adrenal enzyme changes are controlled by pituitary proopiocortin peptides [the putative cortical androgen stimulating hormone (CASH)] is discussed as is the relationship between normal adrenarche and the weight related changes in adrenal function in anorexia nervosa.

Involuntary treatment in anorexia nervosa.

It is difficult to predict, on first contact with patients with AN, whether a compulsory admission to hospital may become necessary to protect their lives and health. There are only tentative pointers so far to an entrenched avoidance of treatment: (1) components of a disordered personality associated with a history of childhood physical or sexual abuse or previous episodes of self-harm and (2) the presence of a more severe illness, suggested by numerous previous admissions. An involuntary admission is likely to be beneficial at least in the short term, as shown by a gratifying weight gain, although a longer period of inpatient stay may be necessary. Patients who have required compulsory detention are at a considerable risk in the long-term as shown by their high mortality rates. It is, therefore, essential to organize long-term observation for all patients who required involuntary admission for AN. A compulsory admission for AN does not require compulsory treatment, such as forced feeding by NGT or other intrusive methods. Clinicians who contemplate a compulsory admission for a seriously ill anorexic patient might therefore question the advantages provided by the detention. First, clinicians can be assured that it should be possible to induce a satisfactory weight gain through persistent nursing methods without running the risk of these patients discharging themselves. With inpatients, the goals are nearly always attained, although the admission may be longer than average. Not only do these patients' nutrition improve vastly, but also they are likely to show improvements in their mental state. Secondly, these patients are likely to learn that the professional staff, their families, and outside agencies take their illness very seriously, even if patients themselves do not seem to. This is particularly evident when patients appeal to a Mental Health Review Tribunal for release. They attend the proceedings and hear the evidence presented by their psychiatrists, the nursing staff, and their nearest relatives. The tribunal usually sustains the compulsory admission: the patient may be initially distressed, but in the long run the experience is generally therapeutic. Finally, compulsory admission permits more stringent forms of supervision. For example, patients who vomit may have legitimately restricted access to bathrooms. Patients addicted to exercise may be rationed to sensibly short periods of walking daily. Patients who are extremely anxious or overactive may be required to take appropriate tranquilizing or sedating drugs, such as one of the benzodiazepine drugs. Clinicians sometimes are reluctant to resort to compulsory admission because of a fear of damaging the therapeutic relationship with their patients. Clinical observations, however, point to the converse being the case, as shown in several studies. Tiller et al maintain: "Compulsory treatment may be an act of compassion: it shows that professionals recognize the severity of the illness and that they are prepared to contain the anxieties provoked by weight gain. Often the patients and their families are immensely relieved to hand over the responsibility, temporarily, to the professional team."

Chemoreception and perception of the bitterness of isohumulones.

Psychophysical experiments were conducted to determine whether isohumulones share a common receptor mechanism with other bitter compounds, and whether parotid saliva flow affects perception of their bitterness. Findings from a study of inter-individual differences in sensitivity to 23 sweet and/or bitter compounds among 25 subjects using the time-intensity (TI) method suggest that isohumulone and tetrahydroisohumulone may share a common receptor mechanism with other bitter compounds except those with the thiourea moiety. Isohumulone and tetrahydroisohumulone displayed a unique dome-shaped TI profile. The bitterness of the two compounds took longer to develop, but it lasted as long as for other bitter stimuli. In a study of the relation between perception of bitterness in beer and parotid saliva flow in 20 young adults, no significant difference was found among the mean saliva flows triggered by 0, 15 and 30 mg/L of isohumulones added to beer, and no significant correlation was found between saliva flow and maximum intensity or total duration of bitterness.

A controlled trial of d-fenfluramine in bulimia nervosa.

A double-blind, placebo-controlled trial of d-fenfluramine in bulimia nervosa was undertaken in order to assess its efficacy in controlling bulimic behavior and relieving more general symptoms. A high proportion of the patients evaluated were reluctant to enter the drug trial in spite of the offer of additional supportive psychotherapy and counselling on dietary control. Moreover, 17 out of the 42 enrolled patients withdrew halfway through the 12 week trial. Were it not for this high rate of defaulting, there might be clearer support for the efficacy of d-fenfluramine in reducing the frequency of overeating and self-induced vomiting in these bulimic patients. An unexpected finding was that among the noncompleters, those on d-fenfluramine had experienced relief of their bulimic symptoms. The persistence of depressive symptoms and features of the eating disorder probably contributed to the noncompleters leaving the trial. Reassuring findings were the absence of weight loss and serious unwanted effects from d-fenfluramine. By itself, d-fenfluramine did not benefit some of the patients with severe bulimia nervosa, but it may yet prove a useful adjunct to psychological treatments.

Metabolic abnormalities associated with skeletal myopathy in severe anorexia nervosa.

The aim of this study was to characterize the metabolic disturbance associated with the skeletal myopathy resulting from extreme weight loss in anorexia nervosa. Muscle function was examined in eight female patients with severe (40%) weight loss due to anorexia nervosa and histologically confirmed myopathy. A wide range of biochemical and hematologic investigations were carried out, including serum enzymes and the response of plasma lactate to ischemic exercise of forearm muscles. All patients showed proximal muscular weakness. A diminished lactate response to ischemic exercise was a consistent finding, and a reduction of serum carnosinase activity was also found. There were no other consistent biochemical or hematologic abnormalities apart from lymphopenia of no clinical consequence. These findings contribute to our understanding of severe protein-energy malnutrition on the musculoskeletal system. The resulting disorder is a metabolic myopathy from which the patients recover rapidly as their nutrition improves. Although the patients admitted to a variety of abnormal eating behaviors, no correlation was found between a specific type of abnormal eating behavior and subsequent biochemical abnormalities. Reinstating appropriate eating behavior will treat the myopathy.

Mutagenic activity of a nitrosated early Maillard product: DNA synthesis (DNA repair) induced in HeLa S3 carcinoma cells by nitrosated 1-(N-L-tryptophan)-1-deoxy-D-fructose.

HeLa S3 cells in suspension were incubated at 37 degrees C with various concentrations of the Amadori compound 1-(N-L-tryptophan)-1-deoxy-D-fructose (Trp-Fru), of its nitrosated analogue NO-Trp-Fru and of sodium nitrite, for varying periods of time, and were assayed for viability (trypan blue exclusion test) and for intracellular DNA, RNA and protein synthesis. None of the compounds tested had any effect on cell viability, or on RNA and protein synthesis apart perhaps from a slightly inhibitory action. While Trp-Fru remained ineffective also as far as intracellular DNA synthesis was concerned, both NO-Trp-Fru and NaNO2 had a major effect on DNA synthesis. With NaNO2, stimulation of DNA synthesis occurred at concentrations above 1 mM in the growth medium, but with NO-Trp-Fru synthesis increased at concentrations below 1 microM. The excess DNA synthesis (i.e. synthesis above control activity) observed with NO-Trp-Fru and also with NaNO2 was due to DNA repair. This was verified by keeping the cells under conditions that prevented normal semi-conservative replication but permitted DNA repair ('unscheduled DNA synthesis'). Two major routes are suggested by which NO-Trp-Fru could damage DNA.

Dynamic headspace analysis of fresh tomato juices.

The methods used to isolate volatile compounds for GC analyses can cause profound effects on the quantitative and qualitative composition of the injected sample, and exert a great influence in the resultant bioactivity of volatiles. Especially with plant tissues like tomatoes, the isolation of volatile constituents using classical methods may yield results which are not representative of the chemicals present in the natural material. Headspace sampling methods may be advantageous in capturing the same volatile compounds emitted from tomatoes that are detected by the human nose. This study utilized an extremely sensitive dynamic headspace sampling with thermal desorption method to determine volatile components of fresh tomato juices. The method proved very sensitive for the isolation of tomato volatiles and concentrations of flavor compounds were much greater than related literature studies.

The influence of 1-(N-L-tryptophan)-1-deoxy-D-fructose [Fru-Trp] and its N-nitrosated analogue [NO-Fru-Trp] on the viability and intracellular synthetic activity (DNA, RNA, and protein synthesis) of HeLa S3-carcinoma cells.

Exposing HeLa S3 cells at 37 degrees C to varied concentrations of, respectively, Fru-Trp (0.1 microM - 1 mM), NO-Fru-Trp (0.1 microM - 1 mM), and NaNO2 (0.6 microM - 6 mM) for varied periods of time (1 - 36 hr) does neither affect their viability (trypan blue dye exclusion test) nor capability to synthesize RNA or protein but is of considerable influence on DNA synthesis in the case of NO-Fru-Trp and NaNO2, but not in the case of Fru-Trp which continues to be ineffective. None of the three compounds tested is of significant influence on cell number. Both NO-Fru-Trp and NaNO2 stimulate DNA synthesis: a maximum of activity [( 3H] thymidine incorporation) exists at the 24 hr time point of incubation, with NO-Fru-Trp, for instance, generating a 2.5-fold increase (over control) at 1 mM concentration in the medium while NaNO2, at comparable concentration, increases DNA synthesis by a factor of 1.6 over control. The increase in DNA synthesis is not due to stimulatory influences on (semi-conservative) DNA replication but represents DNA repair. This was verified by keeping the cells under conditions that prevent normal (semi-conservative) replication but permit repair ("unscheduled DNA synthesis"). Two major routes are suggested by which NO-Fru-Trp could impart DNA damage and, thus, assume mutagenic properties.

Osteopaenia of the lumbar spine and femoral neck in anorexia nervosa.

The bone density in the spine, femoral neck and radius in 31 outpatients with anorexia nervosa (AN) was measured by photon absorptiometry and compared with 31 age matched controls. In all bone sites measured the patients with anorexia nervosa had reduced bone mineral density (spine- control 0.91 + .10 gHA/cm2, AN 0.75 + .09 gHA/cm2; femur- control 0.87 + .09 gHA/cm2, AN 0.67 + .07 gHA/cm2; radius-control 0.41 + .04 gHA/cm2, AN 0.38 + 0.9 gHA/cm2). The mean difference between the groups was greatest in the femoral neck at 0.21 gHA/cm2 (95% CI 0.18-.024 p less than 0.001) and least at the radius 0.04 gHA/cm2 (95% CI 0.02-0.06, p less than 0.05), the lumbar spine was intermediate with a mean difference of 0.16 gHA/cm2 (95% CI 0.12-0.2 p less than 0.001). Femoral and spinal bone mineral density was positively correlated with body mass and negatively correlated with duration of amenorrhoea. Three of these patients had vertebral crush fractures which suggests that this diminution in bone density is of clinical significance.