Enhanced exercise-induced hyperkalemia in patients with syndrome X.

OBJECTIVES: The purpose of this study was to determine whether patients with syndrome X have altered potassium metabolism. BACKGROUND: Patients with syndrome X have angina pectoris and exercise induced ST segment depression on the electrocardiogram despite normal coronary angiograms. Increasing evidence suggests that myocardial ischemia is uncommon in these patients. Altered potassium metabolism causing interstitial potassium accumulation in the myocardium may be an alternative mechanism for chest pain and ST segment depression in syndrome X. METHODS: We compared the magnitude of exercise-induced hyperkalemia in 16 patients with syndrome X (12 female and four male, mean +/- SD age 53 +/- 6 years) and 15 matched healthy control subjects. The participants underwent a bicycle test at a fixed load of 75 W for 10 min, and blood samples were taken for analysis of potassium, catecholamines and lactate before, during and in the recovery period after exercise. In five patients with syndrome X, the test was repeated during alpha1 adrenoceptor blockade. RESULTS: Baseline concentrations of serum potassium, plasma catecholamines and plasma lactate were similar in patients and control subjects. The rate of exercise-induced increment of serum potassium was increased in the patients (70 +/- 29 vs. 30 +/- 21 micromol/liter/min in control subjects, p < 0.001). Six patients, who stopped before 10 min of exercise, showed very rapid increments in serum potassium concentration. Compared to the control subjects, patients also demonstrated larger increments in rate-pressure product, plasma norepinephrine and lactate concentrations during exercise. The rate of serum potassium increment correlated with the rate of plasma norepinephrine increment in the patients (r = 0.63, p < 0.02), but not in the control subjects (r = 0.01, p = 0.97). Blockade of alpha1 adrenoceptors decreased systolic blood pressure at baseline, but did not influence the increment of serum potassium, plasma catecholamines and lactate. CONCLUSIONS: Patients with syndrome X have enhanced exercise induced hyperkalemia in parallel with augmented increases of circulating norepinephrine and lactate. The prevailing mechanisms behind the abnormal potassium handling comprise sources distinct from alpha1-adrenoceptor activation.

Urine and plasma propranolol.

Eight hypertensive patients who had been followed in an outpatient clinic during long-term therapy with propranolol (40 to 160 mg twice daily) were studied during a 24-hr stay in the ward. The usual oral dose was given and the total and free plasma concentrations were determined during the 24 hr and the urinary excretion of unchanged drug was measured. Average free plasma concentration of propranolol (y free) was calculated from: y free = Excreted propranolol (ng/24 hr)/Creatinine clearance (ml/24 hr). There was a significant relationship between log y free and average free plasma concentration (means free) determined from the directly measured plasma concentration curve: log y free = 0.0743 means free - 0.0466 (r = 0.98, P less than 0.001). In another group of propranolol-treated hypertensive patients there was a significant positive relationship between orosomucoid concentration and reciprocal of the free propranolol fraction in plasma. From this relationship the average total drug concentration (y total) was calculated from y free; there was a significant correlation with directly measured total plasma level: log y total = 0.0038 . means total + 1.0895 (r = 0.91, P less than 0.001). It is suggested that individually determined values of y free below 30 ng/ml and y total below 400 ng/ml (the concentration range studied) can be used to calculate the average mean 24-hr free and total plasma concentrations.

Thiopentone-induced changes in the contraction pattern of vascular smooth muscle: the influence of albumin.

The influence of thiopentone on resting tension, contractions evoked by exogenous noradrenaline (NA) and contractions elicited by electrical field stimulation of rings of rabbit pulmonary artery was studied over a concentration range limited by the solubility of the drug. At thiopentone concentrations from 3 X 10(-5) to 1.4 X 10(-3)M in a protein-free electrolyte solution (K-H solution) a gradual increase in resting tension to 232% of the control value was observed. The concentration-effect curve was displaced to the left in the presence of albumin (45 gl-1) at drug concentrations below 1.6 X 10(-4)M. Above that concentration the curve was displaced to the right. The maximal contractile response to exogenous NA in K-H was reduced from 4.1 to 1.8 g by 5.6 X 10(-4)M thiopentone, but the effects of low concentrations of NA were potentiated by thiopentone. The concentration-effect curve for exogenous NA was displaced to the right by albumin itself. The contractions evoked by electrical field stimulation in K-H solution were increased by thiopentone up to 2.4 X 10(-4)M where a maximum of 141% of the control value was reached. Above that a gradual decrease was observed, the height of the contractions being reduced by 75% of the control value at 1.4 X 10(-3)M thiopentone. Thiopentone failed to potentiate electrically-induced contractions in the presence of albumin K-H, and the concentration-effect curve for the inhibitory effect of thiopentone was displaced to the right. 5 From relationships between observed responses and free and total drug concentrations, a procedure was suggested to determine a biologically relevant expression for the thiopentone binding to albumin. The biologically determined albumin binding was always less than the binding determined by equilibrium dialysis, indicating that the fraction of thiopentone bound to albumin could not necessarily be considered biologically inactive.

Antroduodenal motility and gastric emptying. Gastroduodenal motility and pH following ingestion of paracetamol.

The influence of paracetamol on antroduodenal motility and gastric pH was studied in 11 healthy subjects and the relationship between gastroduodenal motility and gastric emptying rate time, tmax, to peak concentration of serum paracetamol, Cmax, was evaluated. The incidence of antral phase III activity and the duration of phase III was diminished with paracetamol (P less than 0.05). The other motility parameters assessed were unchanged. Three patterns of motility and absorption were observed. One group (n = 5) were fast absorbers with a tmax of 1 h and a motility pattern characterized by antral activity, a high motility index and a short duration of phase II (33-60 min); the phase IIIs were complete except in one case. The second group (n = 4) had tmax at 1.5 h and their phase II motility was characterized by a longer duration (80-133 min) (P less than 0.05), by antral activity, and by a high motility index; their phase IIIs were all incomplete. The last group (n = 2) were slow absorbers: Cmax was not reached in the investigation period, no antral contractions were seen, and the motility index was low. The area under the serum-concentration curve of paracetamol differed between the groups at 90 and 180 min (P less than 0.01).

Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans.

Short-term growth hormone (GH) exposure has been shown to stimulate energy expenditure (EE) without concomitant changes in body composition. To what extent this is related to thyroid function, sympathetic activity, hyperinsulinemia, or leptin secretion is unknown. It is also unknown whether the calorigenic effect of GH is influenced by glucocorticoids, which are known to antagonize the anabolic actions of GH. To pursue this, eight normal male subjects (aged 22 to 28 years; body mass index, 21.6 to 26.3 kg/m2) were randomly studied during four 4-day treatment periods with (1) daily subcutaneous (SC) placebo injections and placebo tablets, (2) daily SC GH injections (0.1 IU/kg x d) and placebo tablets, (3) daily prednisolone administration (25 mg morning and evening) plus placebo injections, and (4) daily GH injections plus prednisolone administration. GH administration decreased plasma epinephrine significantly (mean +/- SE, 34.7 +/- 5.7 ng/L for control v 24.8 +/- 5.8 for GH, P < .05), had no effect on plasma norepinephrine or serum leptin, and increased both free triiodothyronine (FT3) levels (5.7 +/- 0.3 pmol/L for control v 6.7 +/- 0.3 for GH, P < .05) and resting EE ([REE] 1,861 +/- 61 kcal/24 h for control v 1,996 +/- 69 for GH, P < .05). Prednisolone administration did not affect epinephrine and REE, decreased norepinephrine (116 +/- 13, P < .05) and FT3 (4.7 +/- 0.2, P < .05), and increased leptin (3.93 +/- 0.71, P < .05). Concomitant GH and prednisolone administration increased REE (2,068 +/- 85, P +/- .05) and leptin (4.82 +/- 0.93, P +/- .05), had no effect on either epinephrine or norepinephrine, and decreased FT3 (5.0 +/- 0.2, P < .05). Resting heart rate (HR) increased only during GH, whereas sympathetic nerve activity was unchanged in all studies. Our data suggest that (1) the calorigenic effect of GH is not mediated by changes in sympathetic activity or leptin secretion, (2) rapid elevations in leptin induced by glucocorticoids do not affect EE in humans, and (3) the acute calorigenic effects of GH are probably related to increased cardiac workload.

The glycaemic index of spaghetti and gastric emptying in non-insulin-dependent diabetic patients.

OBJECTIVE: In the dietary treatment of non-insulin-dependent diabetes mellitus (NIDDM) great interest has been focused on foods with low glycaemic indices. Spaghetti has a low glycaemic index, but in NIDDM the underlying mechanism has not been elucidated. We investigated whether the low glycaemic index in spaghetti was the result of a retarded gastric emptying. DESIGN: Randomized study. SETTING: Department of Endocrinology & Metabolism, Aarhus County Hospital. SUBJECTS: Eight NIDDM in-patients participated without drop-outs. INTERVENTIONS: Paracetamol was used as a marker of the gastric emptying. On three different occasions the patients ingested 40 g of carbohydrate as: (1) spaghetti without paracetamol, (2) spaghetti containing 1.5 g paracetamol, and (3) mashed potatoes with 1.5 g paracetamol added. During the 4 h observation periods blood samples were drawn frequently. The spaghettis were industrially manufactured. RESULTS: The spaghetti meals induced similar glucose and insulin responses. The potato meal induced significantly higher glucose and paracetamol areas [607 +/- 108 vs 284 +/- 54 mmol/l*240 min (P = 0.02), and 18,668 +/- 999 vs 4979 +/- 369 mumol/l*240 min (P < 0.02)] as well as lower emptying index (time(peak)/peak concentration ratio of paracetamol) [2.1 +/- 0.3 vs 0.4 +/- 0.1 (P = 0.001)], as compared with the spaghetti meal. CONCLUSIONS: This study shows that the ingestion of spaghetti was associated with a slower gastrointestinal accessibility of the carbohydrates, which accounts for the low glycaemic index of spaghetti in NIDDM subjects.

Incidence of pulp necrosis subsequent to pulp canal obliteration from trauma of permanent incisors.

Little long-term data are available on the frequency by which pulp canal obliteration (PCO) subsequent to trauma leads to pulp necrosis (PN). In this study, 82 concussed, subluxated, extruded, laterally luxated, and intruded permanent incisors presenting with PCO were followed for a period of 7 to 22 yr (mean 16 yr). At final clinical examination, 51% of the observed teeth responded normally to electric pulp testing (EPT). An additional 40% of the teeth although not responding to EPT were clinically and radiographically within normal limits. Yellow discoloration was a frequent finding. During the observation period, periapical bone lesions suggesting PN developed in seven teeth (8.5%). Twenty-yr pulp survival rate was 84%, as determined from life-table calculations. There was no higher frequency of PN in obliterated teeth subjected to caries, new trauma, orthodontic treatment, or complete crown coverage than intact teeth. Although the incidence of PN in teeth displaying PCO seems to increase over the course of time, prophylactic endodontic intervention on a routine basis does not seem justified.

Rhizomucor miehei triglyceride lipase is processed and secreted from transformed Aspergillus oryzae.

The cDNA encoding the precursor of the Rhizomucor miehei triglyceride lipase was inserted in an Aspergillus oryzae expression vector. In this vector the expression of the lipase cDNA is under control of the Aspergillus oryzae alpha-amylase gene promoter and the Aspergillus niger glucoamylase gene terminator. The recombinant plasmid was introduced into Aspergillus oryzae, and transformed colonies were selected and screened for lipase expression. Lipase-positive transformants were grown in a small fermentor, and recombinant triglyceride lipase was purified from the culture broth. The purified enzymatically active recombinant lipase (rRML) secreted from A. oryzae was shown to have the same characteristics with respect to mobility on reducing SDS-gels and amino acid composition as the native enzyme. N-terminal amino acid sequencing indicated that approximately 70% of the secreted rRML had the same N-terminal sequence as the native Rhizomucor miehei enzyme, whereas 30% of the secreted rRML was one amino acid residue shorter in the N-terminal. The recombinant lipase precursor, which has a 70 amino acid propeptide, is thus processed in and secreted from Aspergillus oryzae. We have hereby demonstrated the utility of this organism as a host for the production of recombinant triglyceride lipases.

Pulp reactions to restoration of experimentally induced crown fractures.

OBJECTIVES: Reattachment of the avulsed enamel-dentine coronal fragment to the remaining tooth structure has become an accepted clinical alternative to a resin composite build-up for the restoration of crown fractured teeth. Since little knowledge exists as to the pulpal response to this procedure, this study was designed to observe the condition of the pulp following experimentally induced crown fracture and restoration in monkeys. METHODS: Experiments were conducted in eight young green Vervet monkeys (Cercopithecus aethiops). In all, 64 fractured incisors were investigated. Light microscopic examination of pulp tissue specimens was carried out after 3 months of observation. RESULTS: The evaluation was restricted to specimens having a fracture plane within 2 mm of the pulp and no pulpal exposure. In general, pulp tissue was well preserved irrespective of the restorative procedure. Even if the restoration or the bonded tooth fragment had been lost during the follow-up period, the pulp generally remained in good condition. Inflammatory infiltrates where seen in only a few specimens and then as clusters of mononuclear leukocytes. Hard tissue repair was frequently observed and displayed various configurations from isolated hard tissue deposits to areas of extensive hard tissue repair in the coronal portion of the pulp. Pronounced hard tissue repair and occurrence of inflammatory cell infiltrates correlated with the presence of stainable bacteria on the fractured dentine surface. CONCLUSIONS: In the absence of direct exposure, reparative dentine is a frequent feature of the pulp's response to crown fracture and restoration with composite or reattachment of the crown fragment with dentine bonding. These restorative procedures appear to ensure continued function of the underlying pulp.

The effect of NaO Li Su on memory functions and blood chemistry in elderly people.

In traditional Chinese medicine a mixture of bee pollen, radix polygoni multiflore, semen ziziphi spinosae, radix salviae multiorhizae, fructus schisandrae and fructus ligustris lucidae, known as NaO Li Su, has a reputation as a remedy against declining memory functions. In the present study the effect of the preparation on failing memory was assessed in 100 elderly Danish volunteers who complained of a deteriorating memory. The study was a double-blind placebo controlled cross-over trial. The effect was evaluated after treatment periods of 3 months' duration by a battery of psychological and biochemical tests. No desirable effects on memory functions were achieved by the active treatment. Increases in the number of red blood cells and in the serum creatinine levels were seen after active treatment. In the subgroup initially showing a number of red blood cells below the median a significant positive correlation was found between changes in the number of red blood cells and changes in the Wechsler Memory Scale scores.

Long-term survival of fragment bonding in the treatment of fractured crowns: a multicenter clinical study.

In three Scandinavian dental facilities, a series of 334 permanent incisors with fractures of the crown or crown and root was treated by reattachment of the fragment with a resin composite. Two centers (Oslo and Stockholm) employed acid etching of enamel alone for fragment bonding (n = 146), while the third center (Copenhagen) used a combination of enamel etching and dentinal bonding (n = 188). Although the final retention rate of fragment bonding was similar in the two groups, it took the dentinal bonding group almost three times as long to drop to 50% fragment retention. This difference could be attributed to greater bonding strength in the dentinal bonding group, greater risk of second injury in the younger acid-etching group, or difficulty in maintaining a dry operative field in the younger age group. The good fragment retention, acceptable esthetics, and pulpal vitality observed in the present series indicate that reattachment of the coronal fragment is a realistic alternative to placement of conventional resin-composite restorations.

[Angiotensin I converting inhibitors in connection with anesthesia and surgery]. / Angiotensin I konverteringshaemmere i forbindelse med anaestesi og operation.

The renin angiotensin system is activated during anaesthesia and operation, and the degree to which this activation takes place depends on the hydration and circulation of the patient. The anaesthetic agent used is also important for the activation. Treatment with ACE-inhibitors blunts or abolishes the sympathetic response to anaesthesia/operation. ACEI treatment reduces the need for other hypotensive agents in controlled hypotensive anaesthesia. Some studies suggest that ACEI-treatment should be continued peroperatively on account of its stabilising effect on the circulation to avoid sudden fluctuations in blood pressure and organ perfusion. On the other hand measurements of the cerebral blood flow under anaesthesia in patients treated with ACEI have shown low values in a few patients and this led the authors to recommend discontinuation before anaesthesia. We conclude that controlled clinical trials to evaluate the haemodynamic and neurohumoral consequences of the interaction between ACEI and anaesthetics are required.

Pulpal healing following acute dental trauma: clinical and radiographic review.

Successful treatment of tooth luxations, crown fractures, and root fractures is often compromised by the emergency nature of the injury. Precise radiographic and clinical evaluation is required to facilitate healing and treatment selection. While traditional treatment protocols indicate that dental injuries implying pulpal ischemia require immediate endodontic therapy to avoid healing complications, the clinical investigations discussed herein suggest that a variety of etiologies for pulp survival/pulp necrosis exist. This article discusses the long-term prognosis of pulp necrosis following traumatic dental injuries, and clinical and radiographic criteria for its diagnosis.