Seven-year follow-up of a randomized clinical trial comparing proton-pump inhibition with surgical therapy for reflux oesophagitis

BACKGROUND: This randomized clinical trial compared long-term outcome after antireflux surgery with acid inhibition therapy in the treatment of chronic gastro-oesophageal reflux disease (GORD). METHODS: Patients with chronic GORD and oesophagitis verified at endoscopy were allocated to treatment with omeprazole (154 patients) or antireflux surgery (144). After 7 years of follow-up, 119 patients in the omeprazole arm and 99 who had antireflux surgery were available for evaluation. The primary outcome variable was the cumulative proportion of patients in whom treatment failed. Secondary objectives were evaluation of the treatment failure rate after dose adjustment of omeprazole, safety, and the frequency and severity of post-fundoplication complaints. RESULTS: The proportion of patients in whom treatment did not fail during the 7 years was significantly higher in the surgical than in the medical group (66.7 versus 46.7 per cent respectively; P=0.002). A smaller difference remained after dose adjustment in the omeprazole group (P=0.045). More patients in the surgical group complained of symptoms such as dysphagia, inability to belch or vomit, and rectal flatulence. These complaints were fairly stable throughout the study interval. The mean daily dose of omeprazole was 22.8, 24.1, 24.3 and 24.3 mg at 1, 3, 5 and 7 years respectively. CONCLUSION: Chronic GORD can be treated effectively by either antireflux surgery or omeprazole therapy. After 7 years, surgery was more effective in controlling overall disease symptoms, but specific post-fundoplication complaints remained a problem. There appeared to be no dose escalation of omeprazole with time.     

Surgical treatment of hyperthyroidism: a ten-year experience.

Hyperthyroidism is treated either by antithyroid drugs, radioiodine (I131) or surgery. In Sweden, surgery is often performed in patients with large goiter or severe hyperthyroidism with infiltrative endocrine ophthalmopathy. To evaluate indications and results of surgical treatment, data from 380 patients operated on for hyperthyroidism at our department during 1986-1995 were analyzed. Twenty-six percent were referred for surgery because of failure of treatment with antithyroid drugs or I131. Ninety-one percent were subjected to subtotal thyroidectomy with a median remnant weight of less than 2 g. In the remaining patients, total thyroidectomy was performed. Transient vocal cord affection occurred in 2.6%, none of which was permanent. Prolonged postoperative hypocalcemia occurred in 3.1%, and permanent hypoparathyroidism in 1%. There was no difference in complication rate between subtotal or total thyroidectomy. In patients with Graves' disease, 5% worsened with regard to ophthalmopathy initially after surgery but later improved. Recurrent disease occurred in 2% of the patients, all of whom had undergone subtotal thyroidectomy. Surgery is not first-line therapy in all patients with hyperthyroidism. However, in experienced hands, surgery is a good therapeutic alternative that can be carried out with no mortality, few complications, and, provided that a minimal remnant is left, very few recurrences.     

Intravenous nicardipine for the treatment of severe hypertension

PURPOSE: Severe hypertension responds to treatment with nifedipine given orally or sublingually. Nicardipine hydrochloride, a water soluble dihydropyridine analogue similar to nifedipine, has less of a negative ionotropic effect and produces less reflex tachycardia than nifedipine. Our purpose was to assess the antihypertensive efficacy and safety of intravenous nicardipine in a group of patients with severe hypertension (defined as a supine diastolic blood pressure of more than 120 mm Hg). PATIENTS AND METHODS: Eighteen patients with severe hypertension received treatment with intravenous nicardipine. Nicardipine titration was performed using doses of 4 to 15 mg/hour to achieve therapeutic goal (diastolic blood pressure 95 mm Hg or less or decrease in diastolic blood pressure of more than 25 mm Hg). After this therapeutic end-point was reached, patients received maintainance therapy with nicardipine for varying lengths of time: one hour (Group I), six hours (Group II), or 24 hours. When blood pressure control was lost, patients in Groups I and II entered a second maintenance period lasting a maximum of 24 hours. Onset and offset of action of nicardipine at various infusion rates and times of infusion were measured. RESULTS: Onset time to achieve therapeutic response was rapid at 15 mg/hour (0.31 +/- 0.13 hours) when compared with lower doses (1.11 +/- 0.36 hours at 4 mg/hour; 0.54 +/- 0.09 hours at 5 mg/hour; 0.52 +/- 0.09 hours at 7 to 7.5 mg/hour). Those who showed a therapeutic response received maintenance infusions with nicardipine for one (n = 7), six (n = 6), or 24 (n = 5) hours. Sustained blood pressure control at a constant rate of nicardipine infusion was seen in all patients during the maintenance period. After discontinuation of nicardipine, the time for offset of action (increase in diastolic blood pressure of 10 mm Hg or more) was independent of duration of infusion. Decreases in both systolic and diastolic pressures correlated well with plasma nicardipine levels. Heart rate increased by about 10 beats/minute, but this increase did not correlate with plasma nicardipine levels. Side effects were minimal, consisting of headache and flushing. In seven patients, local phlebitis developed at the site of infusion. This occurred after at least 14 hours of infusion at a single site, and the incidence can probably be reduced by shortening the infusion time at a single site. CONCLUSION: Nicardipine appears to be a safe and effective drug for intravenous use in the treatment of severe hypertension.     

Increased saliva cortisol awakening response in patients with mild cognitive impairment

BACKGROUND: It is unknown whether HPA-axis dysfunction is present in patients with mild cognitive impairment (MCI). The aim of the present study was to investigate whether cortisol levels are elevated among patients with MCI and/or whether the individuals have adequate feedback control of their HPA axis. MATERIAL AND METHODS: 27 patients with MCI and 15 healthy controls were included in the study. Saliva samplings were performed 5 times a day before intake of 0.5 mg dexamethasone, and 5 times a day after intake of dexamethasone, respectively. RESULTS: Significantly higher cortisol levels were found 15 min after awakening among patients with MCI in comparison with the controls, both before and after dexamethasone administration (p<0.05). Also, the ratio between cortisol at awakening time and 15 min after awakening was lower in the patient group after dexamethasone administration (p<0.05). There were no significant differences in basal cortisol levels before or after dexamethasone between groups. CONCLUSION: The results indicate that there is an HPA-axis disturbance, with normal basal cortisol levels and increased awakening response among patients with MCI. The dissociation between basal values and the awakening response may be of pathophysiological importance for the cognitive impairment.     

cAMP-elevating agents suppress dendritic cell function.

The administration of cAMP-elevating agents affects a number of autoimmune and inflammatory conditions. Because dendritic cells (DCs) play a pivotal role in autoimmunity and inflammation, the isolated effects of cAMP-elevating agents on the function of DCs was examined. In a dose-dependent manner, 8-Bromo cAMP, prostaglandin E(2), and 3-isobutyl-1-methylxanthine inhibited tumor necrosis factor alpha release and suppressed antigen presentation by DCs. The same effect was observed with rolipram, a specific inhibitor of phosphodiesterase type 4, but not with inhibitors of other phosphodiesterases. The decreased antigen presentation by DCs was associated with an enhanced production of interleukin (IL)-10 and with lower major histocompatibility complex type II (MHC II) expression. Furthermore, the inhibition of antigen presentation and MHC II expression was significantly reversed by treatment of DCs with neutralizing antibody against IL-10, suggesting the involvement of an IL-10-dependent mechanism. Taken together, these results might explain why certain cAMP-elevating agents such as rolipram are effective in blocking autoimmunity and inflammation.     

Carotid calcifications in panoramic radiographs are associated with future stroke or ischemic heart diseases: a long-term follow-up study

Clinical Oral Investigations - To assess if carotid calcifications detected in panoramic radiographs are associated with future events of stroke, and/or ischemic heart diseases over...