Metabolism and excretion of citalopram in man: identification of O-acyl- and N-glucuronides

The antidepressant citalopram (CT), a selective serotonin uptake inhibitor, was given in its labelled form, [14C]-CT, as a single oral dose in 50 ml aqueous solution (0.1 mmol/30 microCi/1.1 MBq) to four healthy male volunteers. Concentrations of radioactivity in whole blood and plasma were similar. The respective pharmacokinetic parameters were: Cmax = 214+/-41 and 246+/-69 nmol eq./litre, Tmax = 3 and 2 h, AUC = 18289+/-2959 and 14537+/-2883 nmol eq. h/litre, and t1/2 = 90.2+/-22.5 and 79.5 +/- 14.9 h respectively. A mean of 85.2 +/- 10.4% of the radioactive dose was recovered after 17 days of collection of excreta. The majority of radioactivity was excreted in urine (74.7+/-8.9%) and the remaining part in faeces (10.5+/-2.3%). The HPLC profile of urinary components showed that besides the known metabolites of citalopram, three glucuronides were present. The relative amounts of CT and its metabolites in urine collected for 7 days were: CT (26 %), N-demethyl-CT (DCT, 19%), N,N-didemethyl-CT (DDCT,9%), the N-oxide (7%), the quaternary ammonium glucuronide of CT (CT-GLN, 14%), the N-glucuronide of DDCT (DDCT-GLN, 6%), and the glucuronide of the acid metabolite (CT-acid-GLN, 12%) formed by N,N-dimethyl deamination of CT. CT-GLN was isolated using preparative chromatography and identified by LC-MS-MS and NMR. DDCT-GLN and CT-acid-GLN were identified by LC-MS. This study shows that protracted renal excretion represents the major route of elimination, with a small fraction voided with faeces. A considerable portion of the urinary excreted dose consists of N-glucuronides of CT and DDCT together with the O-acyl glucuronide of CT-acid.     

Characterization of the viral-type nucleotide sequences detected in the RNA of human leukaemic cells by probes of murine and simian origins (author's transl)]

Molecular hybridization techniques were used for searching nucleic acid sequences homologous to murine and simian oncornaviral genomes in the RNA of various categories of human leukaemic cells. We report attempts to characterize the sequences that were detected in defined categories of leukemias. It is shown that: i) although there is some correlation between the two probes used in our study with regard to the positivity or the negativity of the tests for the same leukaemic cases, there are also some discrepancies since some of the cases are positive with one probe and negative with the other; ii) the common sequences of the two probes when isolated, were ineffective to detect any complementary sequences in leukemic cases which were scored as positive when the entire probes were used; iii) the complementary sequences detected in three positive cases of acute myelogenous leukemias by a recycled probe are additive and therefore most probably distributed along the viral genome.     

Abortion as “deviance”

Summary The paper focuses on the relationship between changing societal norms toward women's roles and actual, emotional acceptance of them for oneself, specifically as the norms relate to abortion and sexual behavior. Elective abortion still is regarded by many as a deviant activity. Such a view has sprung from an uncritical acceptance of the traditional role of women. The implications are that women who have abortions accept traditional norms for sexual behavior, in spite of their own sexual activity, and have a generally traditional view of women's roles. They are considered to behave stereotypically and to have failed. Traditional norms for women's roles have been challenged in recent years, however, especially by the feminist movement. The authors hypothesized that women who sought early abortions would tend to have feminist orientations. The paper is based on a study of 1598 women with problem pregnancies, part of a larger study conducted throughout Michigan during 1974–75. The women studied showed little lag in emotional acceptance of changing norms about women's roles. They indicated a non-traditional female role orientation, and seemed to see themselves as competent, selfdirected, and legitimately sexual persons. Most did not have any great conflict over the decision to have an abortion. The findings by and large substantiated the authors' hypotheses.This research is supported by Grant Number 1 RO 1 HD0773901, National Institute of Child Health and Human Development, Washington, D. C.     

Intergenerational change in sex behavior: A belated look at Kinsey's males

This article replicates for Kinsey's male sample the decade-of-birth analyses provided in the Kinsey female volume. Five generations of male respondents are compared in terms of total frequency of sexual activity, and frequency and incidence of nine specific categories of sexual behavior. In general, unmarried males born after 1900 experienced more frequent sexual outlet than did nineteenth-century males. Additionally, the proportion of total outlet devoted to various specific activities varied by birth decade. Solitary masturbation rose somewhat spectacularly in significance with the passing decades, while nocturnal emissions and animal contacts declined. Orgasms provided by heterosexual activities increased slightly for the early twentieth-century generations, but then declined to a point below their nineteenth-century levels. Although homosexual contacts accounted for a constant percentage of total outlet for unmarried males over the five generations, more males in each succeeding generation were actively engaging in homosexual activity, at least on a casual basis. Similarly, although heterosexual contacts accounted for a smaller percentage of all activity among the unmarried in later generations, more of the later-born males had engaged in such activity at least once. For married males, on the other hand, frequency of total outlet was unaffected by generation. A large and stable proportion of this outlet was provided by marital coitus. Although more males in later generations had experienced extramarital contacts, such activities accounted for a small and reasonably stable proportion of total outlet, when frequency of occurrence was considered. Masturbation gained in significance, while nocturnal emissions and homosexual contacts declined, and animal contacts among the married were almost nonexistent in all generations.     

Emergency preparedness: the best defense for major disasters

This article discusses how Silver Cross Hospital in Joliet, Illinois developed its disaster plan and how that plan was successfully tested when a tornado plowed through its service area, causing mass casualties who required both inpatient and outpatient care.     

A phase I trial of continuous-infusion cyclophosphamide in refractory cancer patients

Summary Cyclophosphamide demonstrates enhanced tumoricidal activity with decreased bone marrow toxicity when given on a divided-dose schedule in certain animal models. A total of 22 patients presenting with refractory metastatic cancer were treated in a phase I trial of continuous infusion of cyclophosphamide over 96 h. Granulocytopenia of <500/l that lasted for > 14 days or thrombocytopenia of <25,000/l that lasted for > 14 days was the target dose-limiting toxicity in the absence of nonhematologic grade 4 toxicity. The maximal tolerated dose was 7 g/m². Three patients died. Of 21 evaluable patients, 9 responded, including 8/9 who had experienced disease progression during prior oxazaphosphorine-containing combination chemotherapy. Clinically meaningful responses were observed in patients who had demonstrated clinical resistance to an oxazaphosphorine drug given at lower doses.Supported in part by U.S. Public Health Service grant P01CA-38493 and by a grant from the Mather's Foundation. Two of the authors (J. P. E. and A. D. E.) are recipients of Career Development awards from the American Cancer Society, and one (T. C. S.) is a recipient of a Faculty Development Award from the Pharmaceutical Manufacturer's Association Foundation     

Autobiographical memory in normal aging and primary degenerative dementia (dementia of Alzheimer type)

Autobiographical memory of old people (71-89 years) was studied by a method of free narratives, with normal subjects as well as patients with primary degenerative dementia (SDAT) at three stages of development. The chronological distribution of memories across the life span in both groups showed a peak in adolescence and early adulthood, decrease in mid-life, and increase in recent years. This distribution is different from the results found with the prompt word method among normal old adults, but is similar to the chronological pattern reported for vivid memories. The distribution in the demented group was more flat, which contradicts theories of selective preservation of early memories. With the progression of dementia, autobiographical memory deficits were first evidenced by inaccessibility or loss of memories, and, at a later stage, by loss of details of the retrieved memories and impairment of temporal structure. Events that marked transitions in the lives of the patients ("landmarks") were less subject to forgetting than nontransitional events. The article argues for an approach to autobiographical memory that takes into account sociocultural and developmental determinants of memorability as well as internal mechanisms of the cognitive system.     

Skin flap esophagostomy. A new procedure.

Stoma formation in cervical esophagostomy can be accomplished without tension with the use of cervical skin rotation flaps to form a skin-lined tube. This procedure was performed on six patients; salivary leakage was less, and tube insertion was easier than in patients who had standard esophagostomy procedures. We discuss the indications and contraindications for esophagostomy.     

Health related quality of life in Parkinson's disease: a prospective longitudinal study

OBJECTIVES: To examine the change over time in health related quality of life (HRQL) in a community based cohort of patients with Parkinson's disease. METHODS: One hundred and eleven patients were evaluated for HRQL in 1993 and then again in a follow up study 4 years later. The patients included in the study in 1993 were derived from a prevalence study of patients with Parkinson's disease in the county of Rogaland, Norway. The HRQL was measured by the Nottingham health profile (NHP). At both evaluations clinical and demographic variables were determined during semistructured interviews and by clinical examinations by a neurologist. RESULTS: During the 4 year follow up period there was a significant increase in NHP scores, reflecting a decreased HRQL, in the dimensions of physical mobility, emotional reactions, pain, and social isolation. In the same time period mean total NHP score increased from 120.0 (SD 102.6) to 176.0 (SD 119.4) (p<0.01). There were no clinical or demographic factors found in 1993 that identified patients at higher risk for developing decreased HRQL. Increased UPDRS score (unified Parkinson's disease rating scale) and Hoehn and Yahr stage during the 4 year study period correlated with increased NHP scores. Even though there was no increase in depressive symptoms or self reported insomnia, these symptoms, together with lower Schwab and England score, were the most important factors for a poor HRQL in 1997. CONCLUSIONS: Parkinson's disease has a substantial impact on HRQL. Despite modern care, we found a significantly increased distress during the 4 year follow up period. Increased parkinsonism, measured by UPDRS and Hoehn and Yahr stage, correlated with increased stress, not only in the dimension of physical mobility, but also in the areas of pain, social isolation, and emotional reactions. In addition to the clinical examination, HRQL scoring provides valuable information on the total health burden of Parkinson's disease in both cross sectional and longitudinal evaluations, and contributes to a more comprehensive picture of the total disease impact.