Decrease In Serum Potassium Research Articles

Serum chemistry alterations in Alaskan sled dogs during five successive days of prolonged endurance exercise

To determine the impact of successive days of endurance exercise on select serum chemistry values in conditioned Alaskan sled dogs. Prospective cohort study. 10 conditioned Alaskan sled dogs. All dogs ran 160 km/d for 5 consecutive days. Serum was obtained prior to exercise and immediately after each exercise run; all samples were obtained before dogs were fed. Serum electrolyte, mineral, protein, total bilirubin, urea nitrogen, creatinine, and cardiac troponin-I concentrations and serum alkaline phosphatase, alanine aminotransferase, creatine kinase, and aspartate aminotransferase activities were measured. Data were analyzed by means of analysis of covariance for a randomized complete block design with dog as a blocking variable, time as a covariate, and distance run as the treatment of interest. Least square mean values were compared with values obtained prior to exercise, and linear and quadratic contrasts were examined. Serum globulin concentration was low prior to exercise (mean +/- SD, 2.2 +/- 0.3g/dL) and progressively decreased as exercise continued. Exercise was associated with increases in serum chloride, urea nitrogen, and cardiac troponin-I concentrations and serum alanine aminotransferase, creatine kinase, and aspartate aminotransferase activities and with progressive decreases in serum potassium, total protein, and albumin concentrations. Results suggested that multiple successive days of endurance exercise resulted in mild aberrations in serum chemistry variables in conditioned sled dogs. Changes likely reflected the metabolic stresses of prolonged endurance exercise as well as dietary composition. Hypoglobulinemia in resting, conditioned sled dogs may reflect the immunosuppressive or catabolic effects of intense endurance training.

Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis

Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder in which episodic attacks of muscle weakness occur; they are associated with decreased serum potassium (K+) levels. Recent molecular approaches have clarified that the condition is caused by mutations in the skeletal muscle voltage-gated calcium channel 1 subunit (CACNA1S). We describe two unrelated patients with HypoPP, followed by their relevant clinical studies and gene analysis. Clinical studies included an oral glucose tolerance test (OGTT), food-loading and insulin tolerance tests (ITT). For Case 1, serum K+ levels were extremely decreased following insulin tolerance testing compared with levels for controls. These results support the hypothesis that no efflux of K+ ion occurs in patients because of low activity of adenosine triphosphate (ATP)-sensitive K+ channel (KATP) channels. Mutational analysis of the CACNA1S gene showed a duplicate insertion of 14 base pairs (bp) from 52 to 65 in intron 26, present in the heterozygous state in both patients. No other mutations were detected in the CACNA1S gene, the muscle sodium channel gene (SCN4A) or the voltage-gated K+ channel gene (KCN3) of either patient. Further analysis showed that this duplicate insertion of 14 bp in intron 26 of the CACNA1S gene was found in 23.7% of healthy subjects. K+ dynamics studies are useful for confirming this syndrome, while further gene analysis for various ion channels using amplification and direct sequencing are required to evaluate the molecular basis of the disorder in the individual patient.

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Type 2 Pseudohypoaldosteronism: New Insights Into Renal Potassium, Sodium, and Chloride Handling

Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62 ± 1.8, range; 9–86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 μU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4 ± 0.6 kg/m 2) and serum total protein levels (6.6 ± 0.1 g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.

A Randomized Controlled Trial of Fludrocortisone for the Treatment of Hyperkalemia in Hemodialysis Patients

Previous small uncontrolled studies suggested that fludrocortisone may significantly decrease serum potassium concentrations in hemodialysis patients, possibly through enhancement of colonic potassium secretion. The aim of this study is to evaluate the effect of oral fludrocortisone on serum potassium concentrations in hyperkalemic hemodialysis patients in an open-label randomized controlled trial. Thirty-seven hemodialysis patients with predialysis hyperkalemia were randomly allocated to administration of either oral fludrocortisone (0.1 mg/d; n = 18) or no treatment (control; n = 19) for 3 months. The primary outcome measure was midweek predialysis serum potassium concentration, which was measured monthly during the trial. Prospective power calculations indicated that the study had an 80% probability of detecting a decrease in serum potassium levels of 0.7 mEq/L (0.7 mmol/L). Baseline patient characteristics were similar, except for slightly longer total weekly dialysis hours in the fludrocortisone group (13.0 +/- 1.3 versus 12.1 +/- 1.0; P = 0.02). At the end of the study period, no significant changes in serum potassium concentrations were observed between the fludrocortisone and control groups (4.8 +/- 0.5 versus 5.2 +/- 0.7 mEq/L [mmol/L], respectively; P = 0.10). Similar results were obtained when changes in serum potassium levels over time were examined between the 2 arms by using repeated-measures analysis of variance, with or without adjustment for total weekly dialysis hours. Secondary outcomes, including predialysis mean arterial pressure, interdialytic weight gain, serum sodium level, and hospitalization for hyperkalemia, were not significantly different between groups. There were no observed adverse events. Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and well tolerated, but does not achieve clinically important decreases in serum potassium levels.

Alterations in electrolyte equilibrium in patients with acute leukemia

A wide array of disturbances in electrolyte equilibrium is commonly seen in patients with acute leukemia (AL). These abnormalities present a potential hazard in these patients, as that of enhancing the cardiotoxic effects of certain chemotherapeutic regimens. The literature dealing with AL-related electrolyte abnormalities and their interactions in leukemic patients was reviewed. Sources included MEDLINE and EMBASE. The search strategy was based on the combination of 'acute leukemia', 'electrolyte abnormalities', 'acid-base disorders', 'potassium', 'sodium', 'magnesium', 'calcium', and 'phosphorus'. References of retrieved articles were also screened. A decrease in serum potassium, mainly owing to lysozyme-induced tubular damage, appears to be one of the most frequent and potentially hazardous abnormalities. Other clinically significant metabolic perturbations include hyponatremia and hypercalcemia. A broad spectrum of electrolyte abnormalities is encountered in the clinical setting of AL, which are related to the disease process per se and/or to the therapeutic interventions. Clinicians should be vigilant for early detection and appropriate management of these disorders before the initiation of chemotherapy regimens as well as during treatment.

Effect of Potassium Chloride and Sodium Bicarbonate Supplementation on Thermotolerance of Broilers Exposed to Heat Stress

A t otal of 100-day-old broiler chicken were randomly divided into five groups and kept under elevated temperature (95-98.6 F) to observe the effect of potassium chloride and sodium bicarbonate on the o weight gain, feed conversion ratio (FCR), serum potassium and serum bicarbonate level. Thermostress lead to significant in decrease (P<0.05) weight gain, serum potassium and serum bicarbonate level, while FCR was increased. During heat stress, KCl and NaHCO at levels of 1.5% and 0.5% respectively, improved 3 weight gain, and FCR and significantly increased (P<0.05) serum potassium and bicarbonate level. The results showed that combination of KCl and NaHCO supplementation alleviated the negative effects of heat 3 stress in broilers.

Effect of Oral Glucose Administration on Serum Potassium Concentration in Hemodialysis Patients

Extrarenal potassium disposal is particularly critical in patients with end-stage renal disease. Exogenous insulin stimulates this disposal by enhancing potassium uptake into cells in hemodialysis (HD) patients and healthy subjects. However, the effect of physiological levels of endogenous insulin on this disposal in these patients or healthy subjects is unknown. Effects of an oral glucose tolerance test (37.5, 75, and 150 g) on serum potassium levels were determined in 13 HD patients and 7 healthy controls. Serum potassium and insulin levels and plasma aldosterone and epinephrine levels were measured before and after glucose loads. In HD patients and controls, serum insulin levels increased to a similar magnitude in parallel with increased serum glucose levels, but serum potassium levels decreased significantly only in HD patients. In HD patients, plasma aldosterone or epinephrine levels were not changed significantly after a glucose load. In HD patients, the decrease in serum potassium levels was dependent on the increase in serum insulin levels and was more prominent when 150 g of glucose was administered. In HD patients, the decrease in serum potassium levels correlated negatively (r = -0.45; P < 0.001) with the increase in serum insulin levels, and maximal decrease in serum potassium levels correlated negatively (r = -0.54; P < 0.001) with maximal increase in serum insulin levels. Endogenous production of physiological concentrations of insulin in response to exogenous glucose administration decreases serum potassium levels only in HD patients, independently of plasma aldosterone and epinephrine levels.

Sodium Polystyrene Sulfonate Dosing Guidelines for the Treatment of Adult Hyperkalemia

Standard treatment of hyperkalemia has consisted of the administration of a number of medications including sodium polystyrene sulfonate (SPS) suspension orally or as an enema. Dosage ranges of 15 to 60 g are described in the literature, but specific dosing recommendations based on a patient's serum potassium are lacking. The purpose of this study was to develop a dosing guideline for the oral administration of SPS in the treatment of adult hyperkalemia at our institution. A retrospective review was conducted for adult patients receiving only SPS to treat hyperkalemia during a 3-month period. Serum levels of potassium were recorded prior to and following SPS administration. The retrospective review demonstrated that a 30 g SPS dose resulted in an average decrease in serum potassium of 0.99 mEq/L with a standard deviation (SD) of 0.64. Based on these results, an SPS dose of 30 g was recommended for a serum potassium level greater than 5 mEq/L but less than 6.0 mEq/L in the guidelines. A SPS dose of 60 g was recommended for a serum potassium level of 6 mEq/L or greater. After an internal review in the pharmacy and physician approval, the guidelines were instituted. Clinical outcomes were monitored for 1 month following implementation of the guideline. The prospective analysis resulted in an average decrease of 1.01 mEq/L (SD = 0.67) in serum potassium with a 30 g SPS dose, supporting the guideline.

Application of bilirubin adsorption with HB-H-6 resin plasma perfusion in preoperative for pancreatic cancer with severe obstructive jaundice

目的 探讨HB-H-6树脂血浆灌流吸附胆红素用于恶性梗阻性黄疸病人先期减黄的有效性和安全性.方法对2例胰头癌伴重度黄疸病人用HB-H-6树脂进行血浆灌流减黄,1 d后行胰十二指肠切除术.结果病例1胆红素由533 μmol/L降至347 μmol/L,病例2由454 μmol/L降至367 μmol/L,红细胞、白细胞及血小板下降不明显,血钾、钙、镁有明显降低,但用复方电解质液提前预充冲洗灌流装置可有效减少降低.结论 HB-H-6树脂血浆灌流可以清除胆红素,有望成为恶性梗阻性黄疸先期减黄的新方法。

LOW-DOSE LEVALBUTEROL IN CHILDREN WITH ASTHMA: SAFETY AND EFFICACY IN COMPARISON WITH PLACEBO AND RACEMIC ALBUTEROL

Milgrom H, Skoner DP, Bensch G, Kim KT, Claus R, Baumgartner RA. J Allergy Clin Immunol. 2001;108:938–945Racemic albuterol (RAC) consists of equal parts of (R-) and (S)-albuterol, with all the therapeutic activity being found in levalbuterol (LEV), the (R)-isomer. In addition to lacking bronchodilating activity, (S)-albuterol might have properties, suggested by in vitro studies, that might exacerbate airway reactivity and impair asthma control. The authors sought to determine if LEV results in improved safety and efficacy in children.Children 4 to 11 years old with asthma severity ranging from mild intermittent to moderate persistent were included if baseline forced expiratory volume in 1 second (FEV1) was between 40% and 85% of predicted with at least 15% reversibility to RAC at screening.Children in this multicenter, randomized, double-blind study received 21 days of LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo 3 times daily. Ventolin (GlaxoSmithKline, Research Triangle Park, NC) metered-dose inhalers (MDI) and Nebules (GlaxoSmithKline, Research Triangle Park, NC) were available as rescue medications. The primary endpoint was peak percent change in FEV1 after receiving study medication on day 21. Diary cards were kept, and the Pediatric Asthma Caregiver’s Quality of Life (QOL) Questionnaire was administered at days 0 and 21. Adverse events (AEs), serum potassium and glucose, vital signs, and electrocardiograms were monitored.All 4 active treatments significantly improved the primary endpoint versus placebo (P < .001), with FEV1 immediately after nebulization as follows: placebo, 2.0%; LEV 0.31 mg, 19%; LEV 0.63 mg, 18.1%; RAC 1.25 mg, 12.4%; and RAC 2.5 mg, 15.6%. Both LEV doses led to significantly greater improvement in FEV1 versus RAC 1.25 mg (P < .05). LEV 0.31 mg was the only treatment not significantly different from placebo for changes in heart rate, QTc interval, and glucose. All active treatments decreased serum potassium. There was no evidence of desensitization to either LEV or RAC as measured by FEV1 at day 21 vs day 0. No significant differences were observed among the treatment groups for diary card parameters or QOL. (S)-albuterol did not appear to affect the clearance of (R)-albuterol. In a subset of patients with severe asthma, a dose-response relationship was observed for LEV, indicating that higher doses were more effective.LEV had bronchodilator activity comparable to 4- to 8-fold higher doses of RAC and also demonstrated a slightly better safety profile. LEV should be used as the starting dose in 4- to 11-year-old children with asthma. Patients with more severe asthma might benefit from higher doses.The more favorable therapeutic index for LEV is certainly a valuable feature in children with overtly poor tolerance of RAC and deserves a trial in any child with more severe disease, where response to RAC is suboptimal. There is some suggestion that LEV would be more cost-effective in the hospital setting if it allows for less frequent dosing, as has been claimed. Factors mitigating against the empiric use of LEV first-line, especially at home, include the following: most children overtly tolerate RAC well; AEs noted are generally benign; no MDI form of LEV currently exists; there is a short storage time once a package is opened; and LEV costs much more.

Formoterol (OXIS ®) Turbuhaler ® as a rescue therapy compared with salbutamol pMDI plus spacer in patients with acute severe asthma

Formoterol has a similar onset of effect to salbutamol but a prolonged duration of action. However, the relative efficacy of the two drugs in acute severe asthma is not known. This double-blind, double-dummy study compared the safety and efficacy of the maximum recommended daily dose of formoterol and a predicted equivalent dose of salbutamol in 88 patients presenting to the emergency department with acute severe asthma. Patients were randomized to formoterol 54 μg via Turbuhaler ® or salbutamol 2400 μg via pressurized metered dose inhaler (pMDI) plus spacer in three equal doses over 1 h. Following the full dose, mean FEV 1 at 75 min increased by 37% for formoterol and 28% for salbutamol ( P=0.18). The maximum increase in FEV 1 over 4 h was significantly greater with formoterol compared with salbutamol (51% vs. 36%, respectively P<0.05) and formoterol was as effective as salbutamol at improving symptoms and wellbeing. Both treatments were well tolerated. Formoterol caused a greater decrease in serum potassium (difference –0.2 mmol/l). In severe acute asthma, bronchodilator therapy with high-dose (54 μg) formoterol Turbuhaler provided equally rapid improvements in lung function of greater magnitude over 4 h than high-dose (2400 μg) salbutamol pMDI plus spacer.

Multifactorial insulin resistance and clinical impact in hypertension and cardiovascular diseases

Insulin resistance and hyperinsulinemia have been observed in over 70% of the nonobese, nondiabetic subjects with essential hypertension (HT). Alpha-1 blockers, ACE-antagonists, long-acting Ca blockers including nifedipine CR, some form of β-blockers, tilisolor, which is reported to increase blood flow, improve insulin sensitivity when blood pressure is better controlled. Decrease of serum potassium during insulin sensitivity test and intraplatelet free Ca 2+ concentration is positively and negatively correlated with insulin sensitivity, respectively. Blood pressure is correlated with insulin resistance, which is also observed in secondary HT. The resistance is correlated with salt sensitivity as well as impaired nocturnal fall of blood pressure. These suggest the possible association of insulin resistance with altered intracellular cation metabolism. Insulin resistance and associated hyperinsulinemia have been observed in effort as well as vasospastic angina pectoris (VSAP), atherothrombotic cerebral infarction, and in ASO without obesity, HT, or diabetes, suggesting the resistance resulting from endothelial dysfunction. Insulin resistance has been observed in heart failure and is correlated with angiotensin II. Resistance is also observed in hypertrophic cardiomyopathy and is partially correlated with TNF-α. These results indicate that insulin resistance seem to be multifactorial. An effort to normalize insulin sensitivity is crucial to eliminate multiple risk factors as well as to prevent the progression of atherosclerotic vascular lesions.

Salmeterol 100 μg: an analysis of its tolerability in single- and chronic-dose studies

A combination product containing fluticasone propionate 100 or 250 microg and salmeterol 50 microg has recently been made available in the United States. Some patients, if previously instructed to double their inhaled corticosteroids, may double this product, inadvertently receiving higher doses of salmeterol, potentially causing systemic beta2-agonist-related effects. To examine the systemic effects of single and chronic doses of salmeterol 100 microg. Forty-four studies including a salmeterol 100 microg treatment arm were identified. Data on predictable systemic effects were available in 10 single-dose and 9 chronic-dose studies lasting more than 7 days, in patients with asthma (6 adult, 2 pediatric) or chronic obstructive pulmonary disease (1 study), which were included in a weighted, pooled analysis. Single 100-microg dose studies: mean change from baseline in heart rate was +2.3 beats per minute and systolic blood pressure +0.4 mm Hg. Tremor and palpitations were reported in 5.7% and 2.8%. Other systemic effects included a decrease in serum potassium for 3 subjects (2.1%); an increase in serum glucose, 1 subject (0.7%); and electrocardiographic (ECG) events, 24 cases (17.0%). Twenty-three of these were from one crossover study which reported 27 ECG events after placebo. Chronic dose studies (salmeterol 100 microg): mean change in heart rate and systolic blood pressure were +1.8 beats per minute and -0.2 mm Hg. Tremor and palpitations were reported in 5.6% and 1.7% of 1,504 patients. Thirteen recorded a decrease in serum potassium (0.9%) and 5 an increase in serum glucose (0.3%). Nine patients had ECG events (0.6%). Eight of these were "arrhythmia" from one study, which also reported 12 events before treatment. The mean systemic effects of salmeterol 100 microg are small and of doubtful clinical relevance. Patients (and their caregivers) can be reassured that inadvertently taking double doses of the new combination product are unlikely to affect them adversely.

Low-dose levalbuterol in children with asthma: Safety and efficacy in comparison with placebo and racemic albuterol

Background: Racemic albuterol (RAC) is an equal mixture of (R)-albuterol and (S)-albuterol. Only the (R)-isomer, levalbuterol (LEV), is therapeutically active. Lower doses of LEV, devoid of (S)-albuterol, have demonstrated efficacy comparable to that of higher doses of the (R)-isomer administered as a component of RAC. Objective: The purpose of this study was to determine whether LEV results in improved safety and efficacy in children. Methods: Asthmatic children aged 4 to 11 years (n = 338; FEV1, 40% to 85% of predicted) participated in this multicenter, randomized, double-blinded study and received 21 days of 3-times-a-day treatment with nebulized LEV (0.31 or 0.63 mg), RAC (1.25 or 2.5 mg), or placebo. The primary endpoint was FEV1 (peak percent change). Adverse events, clinical laboratory test results, vital signs, and electrocardiograms were evaluated for safety. Results: All active treatments significantly improved the primary endpoint in comparison with placebo (P < .001). Significant differences in FEV1 were noted immediately after nebulization (median change, 2.0%, 19.0%, 18.1%, 12.4%, and 15.6% for placebo, LEV 0.31 and 0.63, RAC 1.25 and 2.5 mg, respectively; P < .05 vs placebo; P < .05 for LEV 0.31 and 0.63 vs RAC 1.25 mg). LEV 0.31 mg was the only treatment not different from placebo for changes in ventricular heart rate, QTc interval, and glucose (P > .05). All active treatments decreased serum potassium (range, –0.3 to –0.6; P < .002 vs placebo), and RAC 2.5 mg caused the greatest change (P < .005 vs other actives). In a patient subset with severe asthma, a dose-response relationship was observed for levalbuterol, indicating that higher doses were more effective. Conclusion: LEV was clinically comparable to 4- to 8-fold higher doses of RAC, and it demonstrated a more favorable safety profile. LEV 0.31 mg should be used as the starting dose in 4-11 year old children with mild to moderate persistent asthma. Patients with severe disease might benefit from higher doses. (J Allergy Clin Immunol 2001;108:938-45.)

Fludrocortisone for the Treatment of Heparin-Induced Hyperkalemia

OBJECTIVE:To report the use of fludrocortisone for heparin-induced hyperkalemia and to briefly review the available literature relating to heparin-induced hyperkalemia.CASE SUMMARY:A 34-year-old African-American man was admitted to the hospital for pneumococcal pneumonia and sepsis. His hospital course was complicated by the development of acute respiratory distress syndrome, severe sepsis, acute renal failure, placement of a tracheostomy, and recurrent nasopharyngeal bleeding. The patient also developed a subclavian vein thrombosis with extension to the cephalic and basilic veins secondary to placement of a pulmonary artery catheter; anticoagulation with heparin was required. On day 9 of heparin therapy, the patient developed symptomatic hyperkalemia refractory to conventional therapies. Oral fludrocortisone 0.1 mg/d was initiated with resolution of the hyperkalemia within 24 hours despite the continued administration of heparin.DATA SOURCES:A MEDLINE (1966–October 1999) search was performed to identify case reports and clinical trials discussing heparin-induced hyperkalemia or the use of fludrocortisone for hyperkalemia.DISCUSSION:Heparin has the potential to induce hyperkalemia by several mechanisms, including decreased aldosterone synthesis, reduction in number and affinity of aldosterone II receptors, and atrophy of the renal zona glomerulosa. Fludrocortisone promotes potassium excretion by its direct actions on the renal distal tubules. In this patient, fludrocortisone resulted in a significant and rapid decrease in serum potassium even with continued heparin administration and acute renal failure.CONCLUSIONS:This case suggests that fludrocortisone is a reasonable alternative therapy for patients with hyperkalemia secondary to heparin therapy when the continued administration of heparin is necessary.

Angiotensin II type 1 (AT 1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide

The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT 1) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater ( P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP ( < 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough ( P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium ( P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.

Persistent, progressive hypophosphataemia after voluntary hyperventilation

Hyperventilation (HV) and respiratory alkalosis are associated with hypophosphataemia, although the extent and duration of HV required to produce changes in serum phosphate levels are not known. We sought to characterize the effects of HV, with or without dextrose loading, on serum phosphate levels and other biochemical parameters. HV was monitored by controlling the end-tidal partial pressure of carbon dioxide (PETCO(2)). The effect of dextrose was studied because infusion of a glucose load is known to promote a fall in serum phosphate via stimulation of glycolysis. Eight healthy volunteers were enrolled in four study protocols: (1) HV for 20 min to a PETCO(2) of 25-30 mmHg (mild); (2) HV for 20 min to a PETCO(2) of 15-20 mmHg (severe); (3) mild HV with intravenous dextrose loading, and (4) dextrose loading alone. Periodic measurements of serum phosphate, venous pH, serum 2,3-diphosphoglycerate (2,3-DPG) and other parameters were made. Serum phosphate fell during HV and continued to decline after cessation of HV. Dextrose loading alone caused a fall in serum phosphate that continued for at least 30 min after cessation of the infusion (P<0.0002). HV combined with dextrose resulted in a greater decline in serum phosphate than either variable alone (P=0.003). The maximal decline in serum phosphate occurred in severe HV, with a mean decrease of 0.38 mmol/l at 20 min after cessation of HV (P<0.0001). Serum phosphate was still significantly lowered compared with baseline at 90 min after cessation of HV (P=0.001). Other significant changes seen with HV included a decrease in serum glucose (P<0.01), a decrease in serum potassium (P<0.05) and an increase in venous pH (P<0.007). Serum 2, 3-DPG levels did not change significantly in any study protocol. Thus relatively mild acute HV produces significant changes in serum phosphate. In both mild and severe HV this effect is progressive after cessation of HV. This phenomenon has not been shown before, and may have significant clinical implications.

Must we really fear toxicity of conventional amphotericin B in oncological patients?

Fungal infections are an important cause of morbidity and mortality in patients with malignancies. Therefore, the use of amphotericin B (AmB) is essential for these patients. Results from the literature to date show that renal toxicity is the most serious adverse effect of AmB. Renal impairment manifests as a decrease in glomerular filtration and damage to tubular function. Currently, there is no reliable method of preventing nephrotoxicity. We have observed that sodium supplementation alone may not prevent nephrotoxicity. We noted that a large decrease in serum potassium and magnesium was followed by a significant reduction in creatinine clearance and an increase in both serum urea and creatinine. Therefore, we surmised that potassium and magnesium supplements corresponding to the amounts lost by the kidneys, as well as sufficient hydration, are necessary to prevent renal function damage. We decided to test our hypothesis in 32 cancer patients. During AmB therapy, serum electrolyte concentrations and biochemical parameters of renal function and fluid balance were monitored frequently. The daily ion supplementation corresponded to the amount lost through the kidneys. The total duration of administration ranged from 4 to 39 days, with a mean of 13.7 days (median 11.0 days). The mean daily AmB dose was 0.89 mg/kg (median 0.88 mg/kg). The average diuresis was 3863 ml/day, and the median 4000 ml/day. The daily mean i.v.-administered sodium dose was 195.9 mmol, the daily mean dose of i.v. potassium was 103.7 mmol, and the daily mean dose of i.v. magnesium was 9.0 mmol. The frequency of infusion-related side-effects was only 10.0%. These reactions were treated with hydrocortisone. We observed a significant increase in potassium and magnesium lost through the kidneys, and a significant increase in fractional sodium and potassium excretion through the renal tubuli. We did not observe a significant increase in serum creatinine and ion imbalances. Interestingly, the average creatinine clearance did not decrease, but actually increased slightly, though to a statistically insignificant degree, from 1.425 ml/s at the beginning of treatment to 1.589 ml/s on the 20th day of AmB use. Sufficient hydration of patients and ion supplementation corresponding to the amount lost by the kidneys is an effective prophylaxis for prevention of AmB-induced decrease in renal function and for countering imbalances of serum electrolyte concentrations during use of AmB. The frequency of infusion-related side-effects is minimal relative to other reports.

Gating of the L-Type Ca Channel in Human Skeletal Myotubes: An Activation Defect Caused by the Hypokalemic Periodic Paralysis Mutation R528H

The skeletal muscle L-type Ca channel serves a dual role as a calcium-conducting pore and as the voltage sensor coupling t-tubule depolarization to calcium release from the sarcoplasmic reticulum. Mutations in this channel cause hypokalemic periodic paralysis (HypoPP), a human autosomal dominant disorder characterized by episodic failure of muscle excitability that occurs in association with a decrease in serum potassium. The voltage-dependent gating of L-type Ca channels was characterized by recording whole-cell Ca currents in myotubes cultured from three normal individuals and from a patient carrying the HypoPP mutation R528H. We found two effects of the R528H mutation on the L-type Ca current in HypoPP myotubes: (1) a mild reduction in current density and (2) a significant slowing of the rate of activation. We also measured the voltage dependence of steady-state L-type Ca current inactivation and characterized, for the first time in a mammalian preparation, the kinetics of both entry into and recovery from inactivation over a wide range of voltages. The R528H mutation had no effect on the kinetics or voltage dependence of inactivation.