Histories of childhood trauma in adult hypochondriacal patients.

OBJECTIVE: This study examined the childhood histories of trauma, parental attitudes toward health, and physical illness in hypochondriacal adults. METHOD: Sixty outpatients with DSM-III-R hypochondriasis and 60 nonhypochondriacal outpatients from the same general medical clinic were compared. All patients completed the Childhood Traumatic Events Scale and an eight-item questionnaire about childhood illness and health. Medical morbidity was assessed with a medical record audit. RESULTS: Significantly more hypochondriacal than nonhypochondriacal patients reported traumatic sexual contact (28.6% versus 7.3%), physical violence (32.1% versus 7.3%), and major parental upheaval (28.6% versus 9.1%) before the age of 17. These differences remained statistically significant after sociodemographic differences between the groups were controlled for with multivariate regression analysis. The two groups did not differ in the age at which these traumas occurred or in the degree of trauma experienced. Significantly more hypochondriacal patients reported being sick as children and missing school for health reasons, but they did not differ in other measures of childhood illness and parental attitudes toward illness. The two groups had similar levels of aggregate medical morbidity. CONCLUSIONS: Hypochondriacal adults recall more childhood trauma than do nonhypochondriacal patients, even after sociodemographic differences are controlled for. They also recall more childhood illness, although they are not currently more medically sick.

Rate-sensitive inhibition of ACTH release in depression.

Rate-sensitive inhibition of ACTH release is abnormal in Cushing's disease but uncharacterized in depression. The authors found that two of 10 depressed patients had paradoxical responses, suggesting the existence of a hypothalamic-pituitary-adrenal axis abnormality in depression that is independent of dexamethasone suppression test results.

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.

Penetration of carumonam into the pleural fluid: comparison of intravenous bolus and constant infusion in rats with experimentally induced pleurisy.

The penetration of carumonam into the pleural exudate of rats was compared after intravenous administration of 30 mg kg(-1) of the drug as a bolus dose or by continuous infusion over 60 min. Both methods of administration ensured a good penetration of carumonam in pleural exudate, as measured by the areas under the concentration-time curves (AUC). The mean values of the ratio of AUC in exudate to AUC in serum (1.07 +/- 0.11 and 0.96 +/- 0.13 for bolus injection and continuous infusion, respectively) were not significantly different. Administration as a bolus dose resulted in significantly higher peak concentrations in pleural exudate as well as in shorter peak times, whereas continuous infusion produced carumonam levels above the MIC for consistently longer times. The pharmacokinetic parameters obtained by analysis of serum carumonam concentrations proved to be independent of the mode of administration. The foregoing results suggest that carumonam may constitute an effective therapeutic alternative to existing antibiotics for the treatment of pleurisy caused by susceptible organisms. No clear superiority of either method of administration could be established on the basis of pharmacokinetic data.

A cognitive-educational treatment for hypochondriasis.

Hypochondriasis may be conceptualized as a disorder of perception and cognition, in which somatic sensation is experienced as abnormally intense and is then incorrectly attributed to serious medical disease. We describe a therapy to modulate the hypochondriacal patient's somatic sensations, and to alter his or her cognitive appraisal of them, which focuses on four factors that amplify somatic symptoms: (1) attention and expectation; (2) symptom attribution and appraisal; (3) the context used for interpreting the symptoms; and (4) disturbing affect and dependency needs. This therapy, or selected portions of it, can be employed in clinical work with patients individually and in groups, in consultation work, and in more traditional psychotherapeutic settings.

Psychometric validation of two Italian quality of life questionnaires in menopausal women.

OBJECTIVE: To establish the psychometric properties of the Italian version of two quality of life (QOL) questionnaires in menopausal women: the psychological general well being index (PGWBI) and the women's health questionnaire (WHQ). METHOD: These questionnaires were translated into Italian and then self-administered to out-patient women a first time, 1 week later in stable women to assess reproducibility, and 3 months later to evaluate responsiveness over time. Baseline analyses included: factorial structure, multitrait analysis, internal consistency reliability, and clinical validity. RESULTS: Questionnaires were returned by 155 women (median age: 54 years, median duration of amenorrhoea: 56 months, median Kupperman index 26). Principal component analysis (PCA) of the PGWBI showed an important general factor and then, after rotation, three factors. The PCA of the WHQ showed ten factors. Only five reproduced the dimensions postulated à priori quite well. The item convergent validity was confirmed for all items of the major dimension of the two questionnaires, and the item divergent validity, although acceptable, was less satisfying for the PGWBI than the WHQ. The internal reliability was good (Cronbach's alpha > or = 0.70) for the PGWBI and for nine scales out of ten for the WHQ. The six dimensions of the PGWBI and most of the dimensions of the WHQ were significantly correlated to the Kupperman index, indicating the clinical validity of the instruments. The responsiveness to change in clinical status at 3 months was better in the PGWBI than in the WHQ with moderate effect size (around 0.5). CONCLUSION: The Italian versions of the PGWBI and the WHQ are reliable and useful for HRT clinical trials but the dimensional scores must be calculated bearing in mind the limitations in the structure. Other studies are needed to improve the factorial stability of certain WHQ dimensions. For the Italian version of the PGWBI, the validation process is to be completed by studies of mixed populations suffering from other types of disease.

Do women somatize more than men? Gender differences in somatization.

Reviewing the literature of the latter half of the twentieth century, the authors consider the question: do women somatize more than men? The literature review begins with work done in the 1950s in order to look at the phenomenon of somatization as a constellation of symptoms. It encompasses work done in the general community and in the medical arena. The critique of the literature shows why the role of gender in somatizing remains unclear, elucidates inconsistencies, notes the confounding variables, and points out the degree of variable interaction and observer bias. Possible explanations or causes of gender differences are explored. In the present body of literature, women do somatize more than men; however, some of the studies in the literature are flawed. The changing gender difference in medical literature implies that the inquiry at hand concerns the etiology and expression of somatization itself.

Recognizing and treating depression.

The increasing number of antidepressant agents available presents the problem of selecting the right one for a given patient. The choice is guided by the benefits and risks of these drugs within the context of the recommended treatment strategy.

Bioavailability, food effect and tolerability of S-naproxen betainate sodium salt monohydrate in steady state.

S-Naproxen betainate sodium salt monohydrate (naproxen-beta Na, CAS 104124-26-7, Aprenin) in 550 mg capsules (corresponding to 327 mg of naproxen) was administered to 24 healthy volunteers (12 males and 12 females) b.i.d. to steady state in order to check its bioavailability, food interaction and tolerability. Plasma concentrations of naproxen were measured by a well validated HPLC method with fluorimetric detection as a morning pre-dose on days 1 to 6 and in timed samples in three different situations, as follows: a) after the morning dose on day 7 in a fasting status, b) after the evening dose and dinner on day 7 and c) after the morning dose of day 8, taken after a high-fat content breakfast. Pharmacokinetic parameters were evaluated from plasma concentrations by non-compartmental analysis to describe the above three situations. The steady state was reached early, namely by the second day of treatment. The extent of absorption did not differ in the three situations tested, whereas the rate of absorption was fastest in fasting conditions, lowest with the evening dose and intermediate after the high-fat content breakfast. The slow absorption rate of the evening dose was attributed to a circadian rhythm and should allow therapeutically active levels early in the morning, when arthritis pain is particularly tedious. In the three situations explored Cmax, Cmin and AUC were associated with CV % values ranging from 11.7 to 17.2%, which are very low and rare in pharmacokinetic trials. This low variability should allow an accurate estimate of the therapeutic effect expected. Tolerability was checked by objective and subjective symptoms, including vital signs, blood/urine biochemical parameters and occult blood in stools, and proved to be very good. From the comparison of these data with those previously published by other authors who have administered 500 mg of naproxen b.i.d., pre-dose concentrations in a steady state proved to be similar, despite the different doses administered, whereas Cmax and AUC obtained in this study were marginally lower. The kind of food interaction was the same as previously described in literature with naproxen.

Absorption and distribution of naproxen in rats orally treated with naproxen betainate sodium salt monohydrate. Comparison with naproxen.

The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin) was synthesized to improve bioavailability and tolerability of naproxen. 24 albino rats were treated with naproxen-betaNa (84 mg/kg) and 24 with S-naproxen (naproxen) (50 mg/kg) by the oral route, the doses being equimolar. The animals were sacrificed and naproxen was assayed in timed plasma samples drawn off over a 24-h period and in tissues excised 1 h after administration. Peak concentrations of naproxen proved to be higher with naproxen-betaNa than with naproxen as such. The area under the curve of naproxen concentrations observed with the two administrations overlapped as did concentrations of the drug in the lungs, myocardium and liver. Naproxen concentrations in the gastric wall after naproxen-betaNa proved to be lower than after administration of naproxen as such, which allowed the authors to assume that naproxen-betaNa has a better gastric tolerability.

Comparative bioavailability study on naproxen betainate sodium salt monohydrate and naproxen sodium salt in healthy volunteers.

The S-naproxen betainate sodium salt monohydrate (naproxen-betaNa, CAS 104124-26-7, Aprenin, test drug), and the sodium salt of S-naproxen (reference), were administered to twelve healthy volunteers of both sexes according to a crossover design, in a single dose of one 575 mg capsule of test, containing 342 mg of S-naproxen and two 275 mg tablets of reference, containing 502 mg of S-naproxen. Blood samples were drawn off over a 24-h period before (time 0) and after administration at foreseen time intervals. Naproxen was measured in plasma by a validated HPLC assay with UV detection which was able to detect 1 microgram/ml and proved to be linear in the range 1-100 micrograms/ml. The non-compartmental pharmacokinetic parameters obtained were statistically processed according to the EU guidance note on bioavailability and bioequivalence Cmax, AUC0-24h and AUC0-infinity were normalized to the dose of 502 mg of naproxen and log-transformed before statistical analysis to assess bioequivalence. Dose-normalized values of plasma concentrations encountered with the two formulations proved to overlap, with the exception of the first sampling time which showed naproxen concentrations that were higher with test drug than with reference. The specific test for bioequivalence led to 90% confidence intervals within the 80-125% range with target pharmacokinetic parameters, whereas the time to peak (tmax) observed with the test and reference drugs did not differ to any statistically significant degree when analysed with Wilcoxon's non-parametric test. It is concluded that the test drug should be declared bioequivalent with the reference drug in terms of dose-normalized concentrations, despite the more rapid increase in plasma concentrations of naproxen observed at the first sampling time with test drug.