Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.

In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis.     

Effects of oral pergolide mesylate on nociceptive spinal cord reflexes in rats

The effects of orally administered pergolide mesylate on the flexor reflex were evaluated in chronic spinal rats. The mixed D1/D2 agonist pergolide (0.1 to 3.0 mg/kg) produced a dose-related decrease in the magnitude of the flexor reflex elicited by a tetanic stimulus. The effects of pergolide were blocked by haloperidol, demonstrating that the effects of pergolide were mediated through dopamine receptors. In contrast, the selective D2 agonist bromocriptine (3.0 to 30 mg/kg) had no effect on the flexor reflex. The present results are consistent with the interpretation that pergolide produces an antinociceptive action at the spinal cord level by stimulating both D1 and D2 dopamine receptors.     

Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein

The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor-α induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.     

Evaluation of long term thyroid replacement treatment. Swansea Vocational Training Scheme.

A group study was designed to test the need for the continued prescribing of thyroid replacement treatment. Seven doctors who were attending the vocational training scheme at Swansea studied a total of 75 patients. A withdrawal test for 21 days was used to assess the need for continued prescribing of thyroid medication. Sixty per cent (45) of the group studied had had either the wrong diagnosis or an incorrect maintenance dosage, 28% (21) did not need thyroid treatment after the withdrawal test, and 32% (24) had been prescribed an incorrect maintenance dosage of thyroxine as judged by the results of the initial estimation of thyroxine concentration. The medical and economic consequences of an appreciable rate of misdiagnosis and treatment are apparent.     

Glucose tolerance during long term treatment with a somatostatin analogue.

Seven patients with active acromegaly were treated with SMS 201-995, an analogue of somatostatin, for one year, the maximum dose being 100 micrograms three times a day. Three patients had impaired glucose tolerance before treatment, due to insulin resistance in two and insulin deficiency in one. In all patients treatment with the analogue slightly increased postprandial glucose concentrations and suppressed insulin concentrations for two to two and a half hours after each injection; growth hormone concentrations decreased progressively with treatment. The patient with impaired glucose tolerance due to insulin deficiency developed diabetes mellitus after four months'' treatment; concomitant treatment with glibenclamide resulted in a decreased glucose concentration and increased insulin concentration. This analogue of somatostatin had only minor side effects on glucose tolerance in patients with acromegaly and may be used in patients with impaired glucose tolerance provided that glucose concentrations are monitored closely.     

L-tyrosine: a long term treatment of Parkinson's disease

That l-dopa represents a major advance in Parkinson treatment should not hide that a number of problems remain unanswered: on-off effects, transient improvements... Based on the beneficial effects of l-tyrosine in dopamine dependent depressions and narcolepsy, five naive patients diagnosed after sleep polygraphy criteria and five l-dopa and/or dopamine agonist treated patients were prescribed l-tyrosine as a long-term treatment. For some patients, 3 years of L-tyrosine treatment was followed by better clinical results and many fewer side effects than with L-DOPA or dopamine agonists. However, the theoretical long-term sparing neurons potentiality of approach requires further studies.     

Assessing long term backache after childbirth.

OBJECTIVES--To investigate the factors associated with long term backache after childbirth, to assess all women reporting new onset long term backache, and to investigate any relation with pain relief in labour. DESIGN--Data collected from obstetric records and postal questionnaires or telephone interviews on morbidity after childbirth from all women delivering their first baby between March 1990 and February 1991, followed by analysis of data collected from outpatient consultations. SETTING--St Thomas''s Hospital, London. SUBJECTS--Questionnaires were sent to 1615 women who had delivered their first baby in the defined period; 1015 either replied by post or were contacted by telephone. RESULTS--299 women (29.5% of responders) reported backache lasting more than six months and of these 156 (15.4%) said they had had no back problems previously. Those women who had received epidural analgesia in labour were significantly more likely to report new onset backache (17.8%; 95% confidence interval 14.8% to 20.8%) than those who did not (11.7%; 8.6% to 14.8%). Younger women, unmarried women, and those reporting other antenatal symptoms were significantly more likely to report new long term backache. The 156 women reporting new backache were asked to attend an outpatient clinic and 36 (23%) did so. The majority had a postural backache which was not severe. Psychological factors were present in 14 women. CONCLUSIONS--Though new long term backache is reported more commonly after epidural analgesia in labour, it tends to be postural and not severe. There were no differences in the nature of the backache between those who had or had not received epidural analgesia in labour.     

Neuroprotective and neurotrophic effects of long term lithium treatment in mouse brain

Since the worldwide approval of lithium therapy in 1970, lithium has been used for its anti-manic, antidepressant, and anti-suicidal effects. The last decade has witnessed the following discoveries about its neuroprotective and neurotrophic properties, yet the therapeutic mechanisms at the cellular level remain not-fully defined. We have undertaken the present study to determine if chronic lithium treatment, at therapeutically relevant concentrations, exerts neurotrophic/neuroprotective effects in the mouse brain in vivo. For this purpose, 10 months aged mice were fed for 3 months on food pellets contained 1 g (L1 group) or 2 g (L2 group) lithium carbonate/kg, resulting in serum concentrations of 0.4 and 0.8 mM, respectively. The evaluation of lipid peroxidation level and the activities of catalase, superoxide-dismutase and glutathione-peroxidase showed that chronic Li administration, at therapeutic doses doesn’t induce oxidative stress in brain tissue. No changes in the expression levels of molecular chaperones, namely, the HSP70, and HSP90 heat shock proteins and the GRP94 glucose-regulated protein were detected. Moreover, this treatment has caused (1) an increase in the relative brain weight (2) a delay in the age induced cerebral glucose impairment (3) an enhancement of the neurogenesis in hippocampus and enthorinal cortex highlighted by silver impregnation. Under these experimental conditions, no modifications were observed in expression levels of GSK3 and of its downstream target β-catenin proteins. These results suggested that chronic Li administration, at therapeutic doses, has a neuroprotective/neurotrophic properties and its therapeutic mechanism doesn’t implicate GSK3 inactivation.