Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy

Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.     

Health-related quality of life and its predictive role for analgesic effect in patients with painful polyneuropathy.

Painful polyneuropathy is a common neuropathic pain condition. The present study describes health-related quality of life (HRQL) in a sample of patients with painful polyneuropathy of different origin and the possible predictive role of HRQL for analgesic effect. Ninety-three patients with a diagnosis of painful polyneuropathy were included in the analysis. Data were obtained from three randomised, placebo-controlled cross-over studies testing the effect of different drugs on polyneuropathic pain (St. John's wort, venlafaxine/imipramine and valproic acid). Patients completed a HRQL questionnaire (SF-36) after a drug-free baseline period and at the end of each treatment period. At baseline, all eight SF-36 scores were lower than in the normal population. No significant differences were found between SF-36 scales during placebo and treatment with valproic acid and St. John's wort. Those two drugs had not shown a pain relieving effect in former analysis. The SF-36 scale of bodily pain (BP) was improved by venlafaxine treatment (p=0.023). General health (GH) and vitality (VT) were improved under treatment with imipramine (GH: p=0.006, VT: p=0.015). In a multivariate logistic regression analysis, baseline SF-36 scores predicted subsequent response to pharmacological treatment. Results show an impaired HRQL in painful polyneuropathy and suggest that HRQL may predict response to analgesic treatment.     

Conservative treatment for acute rupture of the Achilles tendon

Summary Sixty-six patients with acute ruptures of the Achilles tendon were treated by immobilisation in a plaster cast for 12 weeks. Fifty-seven were followed up for a mean time of 70 months. Four re-ruptures occurred shortly after the initial treatment. Most patients had no or only slight complaints, three had moderate and one severe, problems. The activity level dropped slightly from 5.3 to 5.03 (Tegner score). The results are satisfactory with a low complication rate. The method is an alternative to operative repair, especially in patients declining operation and in those in whom operation or anaesthesia is contraindicated.

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Résumé Soixante-six malades ont fait l'objet d'une étude à long terme concernant le traitement non-chirurgical des ruptures aiguës du tendon d'Achille. Le recul moyen était de 70 mois. Les patients avaient été immobilisés dans un plâtre pendant 12 semaines. 4 ruptures itératives survinrent précocément (6%). La plupart des malades n'avaient pas ou peu de séquelles, trois seulement se plaignaient d'une gêne modérée et 1 d'une gêne importante. Le niveau d'activité avait légérement diminué, de 5.3 à 5.03 (selon le score de Tegner). Les résultats paraissaient satisfaisants dans l'ensemble, avec une taux peu élevé de ruptures itératives ou d'autres complications. La méthode constitue une alternative valable au traitement chirurgical, notamment chez les sujets qui ne veulent pas être opérés ou chez ceux qui présentent des contrindications à l'anesthésie ou à la chirurgie.

     

The Nordic concept of 'faellesskab'.

The complex of cultural, political and societal affiliations, both in a historic and a contemporary perspective, is expressed by a special term in the Nordic languages, 'faellesskab', often with the addition of 'folkelig', as 'folkeligt faellesskab', where 'folkelig' means of the people. No corresponding term exists in English. For medical ethics the concept 'faellesskab', or whatever wording is chosen to serve the semantics of this term, is vital. In research ethics and clinical decision-making complex ethical analyses and normative evaluations are necessary. They cannot be based solely on moral relativism, whether being based on results of opinion polls or on a widespread 'every man minds his own business' concept. 'Faellesskab' possesses the necessary base of common values.     

A chimeric T cell receptor with super-signaling properties

A key question yet to be resolved concerns the structure and function relationship of the TCR complex. How does antigen recognition by the TCR-alphabeta chains result in the activation of distinct signal transduction pathways by the CD3-gammadeltaepsilon/zeta complex? To investigate which part of the TCR-beta chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCR-beta chain with the corresponding TCR-gamma chain domains. We show here that hybridoma cells expressing a chimeric TCR-beta chain (betaIII) containing intracellular and transmembrane TCR-gamma amino acids, together with a wild-type TCR-alpha (alphawt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCR-alphawt/betawt chains. This super-signaling phenotype of the betaIII chain was observed in two different TCRs. One specific for an alloantigen (I-A(bm12)) and one for an autoantigen (I-A(b)/MOG(35-55)). We found that this chimeric alphawt/betaIII TCR had normal association with CD3-gammadeltaepsilon and zeta chains. To investigate the effect of the chimeric betaIII chain in transgenic T cells, we made MOG(35-55)-specific TCR transgenic mice expressing either the alphawt/betawt or chimeric alphawt/betaIII TCR. Similar to what was observed in hybridoma cells, transgenic alphawt/betaIII T cells showed a super-signaling phenotype upon antigenic stimulation. Further studies may help us understand the effect of increased TCR signaling on autoimmunity and may lead to the identification of signaling molecules that can be targeted to stop the progression of autoimmune disorders such as multiple sclerosis.     

Alpers'' disease

Observations on skin reflectance were made on 309 endogamous Indian families, for constitutive (medial upper arm) and facultative skin colour (forehead) to investigate which of the two colours is under a rigid control of genetic action. An assessment of data by coefficient of correlation "r" show that facultative colour is inherited more strictly than the constitutive colour.
Received 4 July, accepted 3 October 1983     

Inflammation as a diagnostic keystone and its clinical implications, exemplified by the inflammatory bowel diseases

Inflammation is a complex process following sublethal injury to tissue and ends with permanent destruction of tissue or with healing. Inflammation has long, long roots in the evolutionary process and as a concept reaches far back in the history of medicine. Inflammation can not be viewed solely in a teleological perspective. Refined by phylogenesis it serves the integrity and survival of groups (species etc.) and not primarily individuals. Inflammation has, in the history of science, been studied on the macroscopic, the microscopic, the dynamic cellular, the immunological, the biochemical/physiological, and the molecular level. Clinicians have for centuries relied on inflammatory signs and symptoms in their diagnostics, even to the extent of being seriously confused, when a subject's inflammatory preparedness is disturbed, as in agranulocytosis, alcoholism, HIV-infection etc. Chronic inflammatory bowel diseases (ulcerative colitis and Crohn's disease) have been studied intensively by inflammologists. The results are partly exchangeable with studies in, for instance, chronic rheumatoid arthritis. They try to answer the over-all question in these diseases: Are we dealing with a normal inflammatory preparedness confronted with a special (unknown) agent, or an abnormal inflammatory preparedness confronted with an ubiquitous agent? The answer will form the basis for the future treatment of these patients, whose diseases remind us of inflammation as man's fellow traveller on "the long phylogenetic march".