The effect of losartan and losartan/hydrochlorothiazide fixed-combination on magnesium, zinc, and nitric oxide metabolism in hypertensive patients: a prospective open-label study

BACKGROUND: Thiazide diuretics and angiotensin-converting enzyme inhibitors can cause excessive urinary zinc (Zn) loss and Zn depletion. Thiazides may also induce magnesium (Mg) deficiency, which may exacerbate hypertension. Data on the effects of angiotensin receptor blockers on Zn and Mg homeostasis are scarce. METHODS: Seventeen hypertensive patients were studied (ten men and seven women, age 50 +/- 3 years, blood pressure 158 +/- 5 / 95 +/- 3 mm Hg). Patients were treated with losartan 50 mg/day for 4 weeks followed by a fixed combination of 50 mg losartan and 12.5 mg hydrochlorothiazide for 4 weeks more. Blood and 24-h urine were collected at baseline and after each study period. Zinc and Mg levels were measured in serum, urine, and peripheral blood mononuclear cells. Nitric oxide metabolites were measured in urine. RESULTS: Treatment with losartan resulted in a significant increase in the urinary Zn/creatinine ratio (from 0.020 +/- 0.004 microg/mg to 0.034 +/- 0.005 microg/mg, P = .02), which was further increased by the losartan/hydrochlorothiazide combination (from 0.034 +/- 0.005 microg/mg to 0.053 +/- 0.008 microg/mg, P = .03). Serum Zn levels were significantly decreased after losartan/hydrochlorothiazide (from 80.0 +/- 4.0 microg/dL at baseline to 74.0 +/- 3.0 microg/dL, P = .007). Peripheral blood mononuclear Zn concentrations were decreased also, but this was not statistically significant. Serum, urinary, and peripheral blood mononuclear Mg levels were not significantly affected by treatment. Nitric oxide urinary metabolites were unchanged throughout the study. CONCLUSIONS: Treatment with losartan causes an increase in urinary Zn excretion and induces Zn deficiency in patients with hypertension. The addition of hydrochlorothiazide has an additive effect. Magnesium and nitric oxide metabolism are not affected by either treatment.     

Current status of treatment of acute leukemia in adults: an overview of the Memorial experience and review of literature

The results of treatment of 629 previously untreated adults with acute leukemia at Memorial Hospital are reviewed. During the past 14 years, 135 adults (greater than 15 years) with acute lymphoblastic leukemia (ALL) have been treated with one of three successive multidrug-intensive treatment protocols (L2, L10/10M, and L17/17M), each calling for 2.5 to 3 years of systemic chemotherapy and prophylactic intrathecal methotrexate without cranial irradiation. The complete remission (CR) rates were L2 (n = 22) = 77%; L10/10M (n = 69) = 86%; L17/17M (n = 44) = 77%. The median durations of survival and remission were, respectively, L2 = 33 and 30 months; L10/10M = 62 months and not reached; and L17/17M = not reached. Almost all relapses occurred within the first 3 years while still continuing treatment, and there were only rate late relapses after stopping treatment. It appears that approximately half of the patients may have been cured with the latest two protocols. During the last 17 years, 494 adults aged 15 to greater than 70 with acute nonlymphoblastic leukemia (ANLL) were treated with one of five successive multiple drug treatment protocols of varying intensity (arabinosylcytosine + 6-thioguanine [n = 36]; L6 [n = 101]; L12 [n = 104]; L14/14M [n = 121]; and L16/16M [n = 132]). Patients with myelodysplastic syndromes generally were not treated until they developed acute leukemia, but were then entered and included in the results. Secondary leukemias following treatment of other neoplastic diseases were not included. The complete remission rates were fairly constant between 47 and 64% and the median durations of remissions were between 9 and 21 months. The intensive treatment L14 and L16 protocols were associated with more early deaths and did not result in a significantly improved remission incidence or duration or survival. With all protocols, the majority of relapses occurred within the first 2 years, but relapses continued to occur at a decreasing rate for 4 years and occasionally even later. Whereas a small fraction (approximately 10 to 15%) of adults with ANLL are now apparently being cured with combination chemotherapy, despite intensive efforts there has been little improvement during the last decade and more selective and effective forms of treatment are urgently needed.     

The Unintended Consequences of Changes in Beverage Options and the Removal of Bottled Water on a University Campus

Objectives. We investigated how the removal of bottled water along with a minimum healthy beverage requirement affected the purchasing behavior, healthiness of beverage choices, and consumption of calories and added sugars of university campus consumers.Methods. With shipment data as a proxy, we estimated bottled beverage consumption over 3 consecutive semesters: baseline (spring 2012), when a 30% healthy beverage ratio was enacted (fall 2012), and when bottled water was removed (spring 2013) at the University of Vermont. We assessed changes in number and type of beverages and per capita calories, total sugars, and added sugars shipped.Results. Per capita shipments of bottles, calories, sugars, and added sugars increased significantly when bottled water was removed. Shipments of healthy beverages declined significantly, whereas shipments of less healthy beverages increased significantly. As bottled water sales dropped to zero, sales of sugar-free beverages and sugar-sweetened beverages increased.Conclusions. The bottled water ban did not reduce the number of bottles entering the waste stream from the university campus, the ultimate goal of the ban. With the removal of bottled water, consumers increased their consumption of less healthy bottled beverages.Bottled water has gained the public’s attention in recent years as towns and universities have banned the sale of bottled water to be more environmentally conscious. Americans use approximately 50 billion plastic bottles each year, 38 billion of which end up in landfills.1 Such bans are instigated to reduce the number of disposable bottles entering the waste stream by convincing consumers to start carrying reusable water bottles or to drink from water fountains instead of purchasing single-use plastic water bottles.1More than 50 colleges and universities have banned the sale of bottled water,1 but little is known about the environmental and health impacts of such bans. According to independent research by the Beverage Marketing Corporation, approximately 73% of the growth in bottled water consumption in recent years has come from those who previously drank caloric drinks, such as soft drinks, juices, and milks.2 Another study by an International Bottled Water Association member company reported that on the basis of an Internet survey of 13 500 consumers, 63% would choose a sugar-sweetened bottled beverage rather than tap water if bottled water was removed from the beverage offerings.2 If these reports are accurate, banning bottled water could lead to an increase in consumers’ calorie and added sugar consumption.Although the causes of excess weight gain are multivariate, there is growing evidence that added sugars, particularly added sugars from sugar-sweetened beverages (SSBs), are large contributors.3–5 Some studies have disputed the connection between SSB consumption and overweight, but the vast majority of research supports an association.6 A 20-ounce soft drink has nearly 17 teaspoons of added sugars, far exceeding the American Heart Association’s recommended limit of 6 teaspoons per day for women and 9 teaspoons per day for men.7 According to National Health and Nutrition Examination Survey data, soft drinks alone are the number 1 single source of calories in the US diet and total SSB consumption contributes 46.2% of the added sugars in the US diet.8,9Ludwig et al. noted that among 548 schoolchildren, for each additional 12-ounce serving of a SSB, the odds of becoming obese increased by 1.6, whereas the increased consumption of diet soda decreased the incidence of obesity.4 Other intervention studies have tried to combat obesity by changing children’s beverage environment. In intervention studies, de Ruyter et al. and Ebbeling et al. found that limiting the consumption of SSBs by providing only bottled water or low-calorie beverages reduced the body mass index (defined as weight in kilograms divided by the square of height in meters), skin-fold thickness, and fat mass of children and adolescents compared with a control group with no intervention.3,10 Although such studies show promising results when SSBs are replaced with low-calorie options, research on the effects of removing bottled water from beverage offerings is limited.3,10We examined how the removal of bottled water on a university campus, along with the implementation of a minimum healthy beverage requirement, affected how many bottled beverages consumers purchased, the healthiness of their beverage choices, and their calorie, total sugar, and added sugar consumption.     

Alternative referent standards for cardiac normality. Implications for diagnostic testing

The radionuclide ventriculographic exercise response was evaluated in three patient populations representing alternative referent standards for cardiac normality: patients with normal coronary arteriograms, healthy volunteers, and uncatheterized patients with a low probability of coronary artery disease. Disease probability was determined by Bayesian analysis of age, sex, symptoms, and the results of cardiac fluoroscopy, exercise electrocardiography, or thallium scintigraphy. A wide range of ventriculographic responses was noted in the 62 catheterized normal patients; 21 (34%) had an abnormal ejection fraction response and 22 (35%) had an abnormal wall motion response. In contrast, the ejection fraction and wall motion responses were normal in the 9 volunteers. In 90 patients (18 catheterized and 72 uncatheterized) who had low disease probability (less than 1%), abnormal responses were rare; the ejection fraction response was abnormal in only 7% and the wall motion response was abnormal in 8%. Thus, these three populations are not equivalent referent standards of normality. Volunteers and patients with low disease probability provide too strict a standard, and their use can overestimate test specificity; catheterized normal patients, on the other hand, provide too lenient a standard, and their use can underestimate test specificity.     

Transcranial magnetic stimulation and auditory hallucinations in schizophrenia

12 patients with schizophrenia and auditory hallucinations received 1 Hz transcranial magnetic stimulation of left temporoparietial cortex. In a double-blind crossover trial, active stimulation significantly reduced hallucinations relative to sham stimulation.     

Prevalence of multivalvular regurgitation in athletes

To assess the effects of exercise training on the prevalence of valvular regurgitation, 2-dimensional echocardiography and Doppler flow mapping were performed in 45 athletes and 26 sedentary control subjects of similar age and sex. Mitral, tricuspid, aortic and pulmonic regurgitations were sought in all possible views and mitral and tricuspid flow velocities were recorded. Mitral and tricuspid anulus diameters and the maximal areas of regurgitant flow were planimetered. Regurgitation of at least one of the cardiac valves was found in 91% of athletes but in only 38% of control subjects (p less than 0.001). Mitral and tricuspid regurgitation occurred more commonly in athletes than in control subjects (mitral 69 vs 27%; tricuspid 76 vs 15%). The prevalence of aortic and pulmonic regurgitation was similar. Although athletes and sedentary normal subjects differed with respect to heart rate, right and left ventricular filling patterns and tricuspid and mitral anulus diameters, none of these variables was related to the presence or severity of regurgitation. Thus, exercise training is associated with an increased prevalence of mitral and tricuspid regurgitation and altered ventricular inflow patterns. The mechanism of these findings is unclear. Multivalvular regurgitation is common in athletes and does not imply structural valvular abnormalities.     

Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study

Testosterone (T) in a hydroalcoholic gel has been developed as an effective and convenient open system for transdermal delivery of the hormone to men. Because the gel can be applied either to small or large areas of skin, it was important to assess whether the skin surface area on which the gel was applied was an important determinant of serum T levels. To answer this question, the pharmacokinetics of a transdermal 1% hydroalcoholic gel preparation of T was studied in nine hypogonadal men. The subjects applied in random order a 25-mg metered dose of T gel either four times at one site (left arm/shoulder) or at four different sites (left and right arms/shoulders and left and right abdomen) once daily (6-8 min) for 7 consecutive days. After 7 days of washout, each subject was then crossed over to the opposite regimen for another 7 days of treatment. Serum samples were collected for measurements of T, 5alpha dihydrotestosterone (DHT), and estradiol before, during (days 1, 2, 3, 5, and 7), and after (days 8, 9, 11, 13, and 15) application of T gel. Multiple blood samples were drawn on the 1st and 7th day after gel application; single samples were obtained just before the next T gel application on other days (24 h after the previous gel application). The T gel dried in less than 5 min, left no residue, and produced no skin irritation in any of the subjects. Mean serum T levels, irrespective of application at one site or four sites followed the same pattern: rising to 2- to 3- and 4- to 5-fold above baseline at 0.5 and 24 h after first application, respectively. Thereafter, serum T levels reached steady state and remained at 4- to 5-fold above baseline (at the upper limit of the normal adult range) for the duration of gel application and returned to baseline within 4 days after stopping application. The application of T gel at four sites (application skin area approximately four times that of one site) resulted in a mean area under the curve (AUC0-24h) for serum T levels on the 7th day (868 +/- 72 nmol*h/L, mean +/- SEM), which was 23% higher but not significantly different (P = 0.06) than repeated application at one site (706 +/- 59 nmol*h/L). This could be due to the limited number of subjects studied (n = 9). Mean serum DHT levels followed the same pattern as serum T, achieving steady-state levels by 2 days. The mean concentration of serum DHT on the 7th day was significantly higher after application at four sites (9.15 +/- 1.26 nmol/L, P < 0.05) than at one site (6.9 +/- 0.77 nmol/L). These serum DHT levels were at or above the normal adult male range. Serum DHT:T ratio was not significantly altered by T gel application. Serum estradiol levels followed the same pattern as serum T and showed no significant difference between the one- or four-site application. We conclude that transdermal daily application of 100 mg T gel resulted in similar steady levels of serum T. The surface area of the skin to which the gel was applied had only a modest impact on serum T and DHT levels. Mean serum levels of T and DHT was higher by 23% and 33%, respectively, despite application of the gel to four times the skin area in the four sites compared with the one site group. Because of the greater dosage flexibility provided, hydroalcoholic T gel application over multiple sites seems to be an effective and nonskin-irritating method of transdermal T delivery for hypogonadal men. Dose-ranging studies are required to determine dosage regimens for T gel application as a replacement therapy in hypogonadal men.     

Thoracic splenosis: A diagnosis by history and imaging

Abstract:   Thoracic splenosis (TS) is autoimplantation of ectopic splenic tissue in the thoracic cavity that occurs following splenic injury. The majority of cases of TS are asymptomatic and are diagnosed in the course of an evaluation of incidentally discovered pulmonary lesions. Some cases may be difficult to diagnose, especially if features suggesting TS are not recognized. This may lead to an extensive work-up and unnecessary invasive diagnostic procedures including thoracotomy. This case report describes a 40-year-old man, who was diagnosed incidentally with TS, several years after the initial injury. Multiple, asymptomatic, left-sided pleural based lesions associated with a history of thoracoabdominal injury and splenectomy are the key points that should alert suspicion of TS, which can then simply be confirmed by a Tc-99m sulphur colloid radionuclide scan. Most patients are treated conservatively unless they are symptomatic. Physicians must recognize the key features suggesting a diagnosis of TS, order appropriate imaging studies and avoid unnecessary invasive diagnostic procedures.     

Reviews of acupuncture for chronic neck pain: pitfalls in conducting systematic reviews

This paper examines some of the problems specifically associated with conducting research into acupuncture and how this can lead to further problems with subsequent systematic reviews. Studies for the treatment of chronic neck pain have been used as examples of how presented information can be misleading to an acupuncture-naive reader and how researchers must be sensitive to these problems when compiling their inclusion and exclusion criteria. The problems associated with scoring trials are discussed and further work to increase the scope of scoring mechanisms is recommended in order to produce meaningful systematic reviews in the future.