Biomedical subjects
T Friedman
Publications and source records attributed to T Friedman.
Psychopathology in patients with endogenous Cushing's syndrome: 'atypical' or melancholic features.
OBJECTIVE: Prolonged elevations of glucocorticoids have been linked to the effective disturbances experienced by patients with Cushing's syndrome. Major depression has been most commonly reported in patients with endogenous Cushing's syndrome. The purpose of this study was to determine whether these patients experience melancholic or 'atypical' subtype depression and to determine relations between current psychological functioning and factors such as duration and severity of Cushing's syndrome. DESIGN AND PATIENTS: We examined 33 adult patients with documented Cushing's syndrome and 17 hospitalized, matched controls, using standardized structured interviews and tests. RESULTS: During the active phase of Cushing's syndrome (prior to and/or on admission), 66.7% of all patients reported histories meeting criteria for a psychiatric diagnosis. Of those with a diagnosis during Cushing's syndrome, 50% reported major depression. Upon presentation to this institution, atypical depression was the most common diagnosis involving 51.5% (n =17) of all enrolled patients. Of the 17 with atypical depression, 8 reported a co-morbid psychiatric disorder. The duration of Cushing's syndrome was an important factor in predicting whether patients sought psychological intervention or met criteria for psychiatric diagnosis. CONCLUSION: Patients with active endogenous Cushing's syndrome exhibit significant psychopathology expressed primarily by atypical depression. Longer duration of Cushing's syndrome may place them at increased risk of such psychopathology.
Antidepressants in pregnancy and breastfeeding.
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Maintenance of the hydrophobic face of the diphtheria toxin amphipathic transmembrane helix 1 is essential for the efficient delivery of the catalytic domain to the cytosol of target cells.
The transmembrane (T) domain of diphtheria toxin (DT) comprises nine alpha-helices and has been shown to play an essential role in the efficient delivery of the catalytic (C) domain of DT across the eukaryotic cell membrane and into the cytosol. We have demonstrated recently that the first three amphipathic helixes of the T domain, although not necessary for either channel formation or receptor binding, are required for the efficient transmembrane delivery of the C domain. In the present study, we have performed a detailed structure-function analysis of T domain helix 1 (TH1) of the DT-related fusion protein DAB389IL-2. We performed exchange and site-directed mutagenesis of TH1 and the resulting mutant fusion toxins were analyzed by gel electrophoresis and tested for their efficiencies in the delivery of the C domain to the cell cytosol. We demonstrate that the overall charge distribution and hydrophobicity of amino acids in the amphipathic helix TH1, rather than a specific amino acid sequence, are critical for the function of this helix. The insertion of a charged residue in the hydrophobic face of TH1 abolishes cytotoxic activity, whereas replacement of a hydrophobic residue by a charged amino acid in the hydrophilic face of the helix has little, if any, effect on cytotoxic activity. In addition, we have identified Ser220 by site-directed mutagenesis as a residue that appears to be critical for correct folding of the fusion toxin. Mutations in this position result in fusion proteins that are extremely sensitive to proteolytic attack.
Multiple personality disorder following childbirth.
A case of multiple personality disorder is described as a coping mechanism protecting the patient from the abuse to which she was subjected throughout her life. The multiple personalities became more prominent following the birth of a severely handicapped child.
Care of women with puerperal psychiatric disorders in England and Wales.
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The study of psychological factors in couples receiving artificial insemination by donor: a discussion of methodological difficulties.
Artificial insemination by donor (AID) may be the only means by which many infertile couples are able to have a child. However, the treatment is not invariably successful and it is postulated in the literature that psychological factors may be implicated when conception does not occur. Further investigation is required to establish the nature of any relationship between psychological stress and conception after AID but designing an adequate study is confounded by many methodological difficulties. These include issues relating to ethics, recruitment, measurement and logistics. In this paper, such aspects are examined and the importance of research in this field for nursing is highlighted.
Infertility and assisted reproduction.
The inability to have children is a considerable cause of human distress. There is little evidence to suggest that the vast majority of infertile couples differ in their premorbid psychological make-up from their fertile contemporaries. There is understandable grief in response to their loss of the ability to have children and in vulnerable people this may be profound. There is little known of the long-term outcome of such couples, but it seems likely that for some it will be a devastating experience that will affect their life-time mental health. There are a large proportion of couples with unexplained infertility, but there is little evidence that this diagnosis is particularly associated with psychological factors, although research continues into possible links between stress and hormones that affect the reproductive system, such as prolactin. Artificial insemination and IVF have particular problems, not only due to conception occurring out of normal sexual intercourse. In artificial insemination using donor sperm the problems of a genetically different father has similarities with the debate about egg donation for IVF. These technical procedures are undoubtedly stressful but generally, as for other treatments, if they are successful the rewards appear to outweigh any misgivings of the couples involved. There is a need for further research as to whether psychological factors are causative in infertility as the absence of any link might indeed be reassuring to couples. We would also benefit from knowing the long-term outcome of couples for whom treatment is not successful.
Distress caused by miscarriage.
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The psychiatric consequences of spontaneous abortion.
Sixty-seven women were interviewed four weeks after spontaneous abortion. As determined by the Present State Examination, 32 of these women were psychiatric cases. This rate is four times higher than in the general population of women. In each case the diagnosis was depressive disorder, a finding confirmed by scores on three depression rating scales. Many women showed typical features of grief. Depressive symptoms were significantly associated with a history of previous spontaneous abortion, and less so with childlessness.
Women's experiences of general practitioner management of miscarriage.
A study of 67 women one month after miscarriage identified significant levels of dissatisfaction with their medical care. There are particular problems in managing miscarriage which is very distressing for many women but a common clinical presentation for doctors. The reasons for women's dissatisfaction with their management are explained. Greater understanding of the experience of miscarriage should lead to better management and suggestions are made for better care for this common distressing experience.
Giant papillary conjunctivitis following cataract extraction.
Out of a series of 600 cataract extractions, 14 patients were found to have giant papillary conjunctivitis (GPC) due to 10-0 nylon sutures. When renewed conjunctival irritation appears weeks or months after surgery, GPC should be suspected and confirmed by eversion of the upper eyelid at the slit lamp. Free edges of protruding corneoscleral nylon sutures should be looked for. Signs and symptoms of GPC disappear within one to four weeks after removal of the offending suture.
Hypoxanthine: guanine phosphoribosyltransferase mutants in Saccharomyces cerevisiae.
Yeast mutants lacking activity of the enzyme hypoxanthine:guanine phosphoribosyltransferase (H:G-PRT) have been isolated by selecting for resistance to 8-azaguanine in a strain carrying the wild type allele, ade4%, of the gene coding for amidophosphoribosyltransferase (PRPPAT), the first enzyme of de novo purine synthesis. The mutants excrete purines and are cross-resistant to 8-azaadenine. They are recessive and represent a single complementation group, designated hpt1. Ade4-su, a prototrophic allele of ade4 with reduced activity of PRPPAT, is epistatic to hpt1, suppressing purine excretion and resistance to azaadenine but not resistance to azaguanine. The genotype ade2hpt1 does not respond to hypoxanthine. Hpt1 complements and is not closely linked to the purine excreting mutants pur1 to pur5. Hpt1 and pur6, a regultory mutant of PRPPAT, are also unlinked but do not complement, suggesting a protein-protein interaction between H:G-PRT and PRPPAT. Mycophenolic acid (MPA), an inhibitor of de novo guanine nucleotide synthesis, inhibits the growth of hpt1 and hpt1+. Xanthine allows both genotypes to grow in the presence of MPA whereas guanine only allows growth of hpt1+. Activity of A-PRT, X-PRT and H:G-PRT is present in hpt+. Hpt1 lacks activity of H:G-PRT but has normal A-PRT and X-PRT.
Immunofluorescent localization of Tamm-Horsfall mucoprotein.
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Antidepressants.
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Tranquillising actions.
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