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OBJECTIVE: The aim of the study was to elucidate whether combustion of skeletal muscle glycogen during a very low calorie diet (VLCD) was associated with decreased muscle potassium content. A comparison between different methods was also performed to evaluate body composition during a VLCD and a low calorie diet (LCD). DESIGN: Dietary treatment of obese women by VLCD and LCD. Measurements after 1 and 2 weeks of VLCD and 6 months of LCD. SUBJECTS: Fifteen perimenopausal obese women aged 46.5±1.3 y and 15 of 48.0±0.7 y of age. MEASUREMENTS: Skeletal muscle biopsies under local anaesthesia. Body composition measurements by means of deal-energy X-ray absorptiometry (DEXA), and measurements of total body potassium ([sup 40]K) and total body nitrogen (TBN). Measurements of electrolytes and glycogen concentration in muscle samples. RESULTS: In the first study (1 week of VLCD) skeletal muscle glycogen decreased (P<0.01), but muscle potassium increased (P<0.01). Muscle sodium decreased (P<0.01), while muscle magnesium was unaltered. Body weight decreased by 2.9±0.5 kg and [sup 40]K decreased. Fat-free mass (FFM) calculated from [sup 40]K and DEXA decreased by 2.7 vs 1.9 kg (P<0.001). Body fat measured with DEXA decreased by 1.1 kg (P<0.01), but not body fat calculated from [sup 40]K. TBN decreased by 0.03±0.01 kg (P<0.05) and FFM calculated from TBN by 2.9±0.5 kg (P<0.002). In the second study, 6 months on the LCD resulted in 17.0±2.0 kg weight reduction and this was mainly due to reduced body fat, 14.0±2.0 kg measured with DEXA and from [sup 40]K (P<0.001). The decrease in FFM was slight. CONCLUSION: One week of VLCD resulted in muscle glycogen depletion but increased muscle potassium content in spite of decreased total body potassium. FFM contributed to the main part of body weight loss during short periods of severe energy restriction, but remained unchanged during long-term dietary treatment. Body fat became mostly... [ABSTRACT FROM AUTHOR]

The relation between blood pressure and skeletal muscle magnesium and potassium, and the relation between these electrolytes and body mass index, blood lipids, blood glucose and plasma insulin concentrations were studied in 29 hypertensive and 21 normotensive men. In addition, a comparison was made between the normotensive men and 37 normotensive women regarding the concentrations of muscle potassium and magnesium. Mean skeletal muscle potassium concentration was lower and plasma insulin higher in hypertensives compared to normotensives. Systolic and diastolic blood pressures were inversely correlated to muscle potassium and positively correlated to insulin. Muscle magnesium was positively correlated to muscle potassium but not to blood pressure. Muscle magnesium was significantly higher in normotensive women, compared to normotensive men. Muscle potassium did not differ between the genders. [ABSTRACT FROM AUTHOR]

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity. [ABSTRACT FROM PUBLISHER]

One hundred and sixty consecutive patients less than 50 years of age (mean 38 years) referred for long term electrocardiographic recording were evaluated retrospectively. Significant cardiac arrhythmias were detected in 51 of 107 (48%) patients examined because of syncope or dizzy spells or both. Of 39 patients examined for cardiac complaints or presumed complex arrhythmias, 15 (38%) had significant arrhythmias. Of 14 patients examined because of otherwise unexplained strokes, nine had slow sinus rates. Of these, one patient had recently undertaken moderately intensive athletic activity and four had been undertaking vigorous athletic activities for several years. All of the 12 active athletes who were followed up on account of syncope or dizzy spells were free of symptoms after reducing their athletic activities. The cardiac rhythm returned to normal in four out of five who underwent repeat long term electrocardiographic recording. It is suggested that vigorous athletic activity in subjects of 30-50 years of age may transform the adaptative bradycardia of the athlete into a condition similar to the embolising sick sinus syndrome. [ABSTRACT FROM PUBLISHER]

The impact of coronavirus disease 2019 challenged schools and credential programs to adjust pedagogy, but rapid changes impeded equitable practices to K-12 grade English Learners (ELs). The framework stems from critical multicultural education. Data represented 81 credential candidates across three universities. Study confirmed that ELs lacked access to online learning, active engagement with peers/teachers, and differentiated instruction due to rapid changes and uncertainties to their programs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Providing clinicians with objective outcomes of neuromodulation therapy is a key unmet need, especially in emerging areas such as epilepsy and mood disorders. These diseases have episodic behavior and circadian/multidien rhythm characteristics that are difficult to capture in short clinical follow-ups. This work presents preliminary validation evidence for an implantable neuromodulation system with integrated physiological event monitoring, with an initial focus on seizure tracking for epilepsy. The system was developed to address currently unmet requirements for patients undergoing neuromodulation therapy for neurological disorders, specifically the ability to sense physiological data during stimulation and track events with seconds-level granularity. The system incorporates an interactive software tool to enable optimal configuration of the signal processing chain on an embedded implantable device (the Picostim-DyNeuMo Mk-2) including data ingestion from the device loop recorder, event labeling, generation of filter and classification parameters, as well as summary statistics. When the monitor parameters are optimized, the user can wirelessly update the system for chronic event tracking. The simulated performance of the device was assessed using an in silico model with human data to predict the real-time device performance at tracking recorded seizure activity. The in silico performance was then compared against its performance in an in vitro model to capture the full environmental constraints such as sensing during stimulation at the tissue electrode interface. In vitro modeling demonstrated comparable results to the in silico model, providing verification of the software tool and model. This study provides validation evidence of the suitability of the proposed system for tracking longitudinal seizure activity. Given its flexibility, the event monitor can be adapted to track other disorders with episodic and rhythmic symptoms represented by bioelectrical behavior.Clinical relevance-An implantable neuromodulation system is presented that enables chronic tracking of physiological events in disease. This physiological monitor provides the basis for longitudinal assessments of therapy outcomes for patients, such as those with epilepsy where objective identification of patient seizure activity and rhythms might help guide therapy optimization. The system is configurable for other disease states such as Parkinson's disease and mood disorders.

Brain stimulation therapies have been established as effective treatments for Parkinson's disease, essential tremor, and epilepsy, as well as having high diagnostic and therapeutic potential in a wide range of neurological and psychiatric conditions. Novel interventions such as extended reality (XR), video games and exergames that can improve physiological and cognitive functioning are also emerging as targets for therapeutic and rehabilitative treatments. Previous studies have proposed specific applications involving non-invasive brain stimulation (NIBS) and virtual environments, but to date these have been uni-directional and restricted to specific applications or proprietary hardware. Here, we describe technology integration methods that enable invasive and non-invasive brain stimulation devices to interface with a cross-platform game engine and development platform for creating bi-directional brain-computer interfaces (BCI) and XR-based interventions. Furthermore, we present a highly-modifiable software framework and methods for integrating deep brain stimulation (DBS) in 2D, 3D, virtual and mixed reality applications, as well as extensible applications for BCI integration in wireless systems. The source code and integrated brain stimulation applications are available online at https://github.com/oxfordbioelectronics/brain-stim-game.

Unlabelled: The association between leptin and areal BMD has been controversial, and the predictive role of leptin on cortical volumetric BMD and bone size has not previously been studied. We show that leptin is a negative independent predictor of aBMD (DXA), at several measured sites, and of cortical bone size (pQCT) in a large population of young men., Introduction: Recent findings suggest that both adipose tissue (AT) and bone mass are regulated by leptin. Previous reports studying the association between leptin and areal BMD (aBMD) have yielded conflicting results. The role of leptin on volumetric BMD (vBMD) and bone size of the cortical and trabecular bone compartments has not previously been studied., Materials and Methods: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a population-based study of 1068 men (age, 18.9 +/- 0.6 [SD] years). aBMD of the total body, lumbar spine, femoral neck, both radii, and trochanter, as well as total body AT and lean mass (LM) were measured using DXA, whereas cortical and trabecular vBMD and bone size were measured by pQCT., Results: Total body LM could explain a larger magnitude of the difference in the variation in aBMD and cortical bone size than what total body AT could (total body aBMD: LM 37.4% versus AT 8.7%; tibia cross-sectional area [CSA]: LM 46.8% versus AT 5.6%). The independent role of leptin on bone parameters was studied using a multiple linear regression model, including age, total body LM and AT, height, present physical activity, calcium intake, and smoking as covariates. Leptin was found to be a negative independent predictor of aBMD (total body: beta = -0.08, p = 0.01; lumbar spine: beta = -0.13, p < 0.01; trochanter: beta = -0.09, p = 0.01), as well as of the cortical bone size (CSA and thickness) of both the radius (CSA: beta = -0.12, p < 0.001) and tibia (CSA: beta = -0.08, p < 0.01), but not of the cortical or trabecular vBMD of these bones., Conclusion: Our results indicate that LM has a greater impact on bone mass than AT. Our findings further show that leptin is a negative independent predictor of aBMD at several measured sites and of bone parameters reflecting cortical bone size, but not vBMD, in a large population of young Swedish men.

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment., (Copyright 2003 S. Karger AG, Basel)

The few trials in GH-deficient (GHD) adults that have investigated the long-term effects of GH-replacement therapy on insulin sensitivity have shown conflicting results. In this study, insulin sensitivity was determined using the hyperinsulinemic, euglycemic clamp technique in 11 GHD adults at baseline and after 6 months, 1 yr, 2 yr, and 7 yr of GH-replacement therapy. Furthermore, insulin sensitivity in the GHD patients was compared with that in 11 matched control subjects at baseline and with that in 11 other matched controls at study end. The mean initial GH dose was 1.10 mg/d. The dose was gradually lowered; and after 7 yr, the mean dose was 0.61 mg/d. A sustained reduction in body fat and a sustained increase in fat-free mass were observed. Serum high-density lipoprotein-cholesterol (HDL-C) increased, and serum low-density lipoprotein-cholesterol (LDL-C) decreased, after 7 yr of treatment. Fasting blood glucose was transiently increased during the first year of GH replacement. The glucose infusion rate/body weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp technique, was unaltered during GH-replacement therapy. The comparisons with the control subjects revealed that GIR/BW in the GHD patients was 45% of that in the control subjects at baseline; whereas, at study end, the GIR/BW was 71% of that in the control subjects (P = 0.06 vs. baseline). This could suggest that GH-replacement therapy may prevent the age-related decline in insulin sensitivity in GHD patients.

In recent years, there has been a resurgence of interest in interstitial radiation as a cost-effective and efficient method of treating organ-confined prostate cancer. We describe our 7- and 8-year results with transperineal Iodine-125 and Palladium-103 implantation. A total of 551 consecutive patients were treated. Of these, 320/551 (58%) received implant alone (Group I), and 231/551 (42%)--considered higher risk patients--were also treated with a modest dose (45 Gy) of external beam irradiation (Group II). The median follow-up for Group I was 55 months, and for Group II, 60 months. At 7 years, the actuarial freedom from biochemical failure (prostate-specific antigen (PSA) < or = 1.0 ng/mL) was 80% in Group I patients, and, at 8 years, 65% in Group II patients. Morbidity was minimal if patients had not undergone prior transurethral prostate resections. The results indicate that interstitial radiation is a valid treatment for clinically localized prostate cancer.

Background: Prostate cancer, suspected by serum prostate-specific antigen (PSA) elevation and/or digital abnormalities, is not always evident on gray-scale or color Doppler transrectal ultrasound (TRUS). EchoGen (Sonus Pharmaceuticals, Inc., Bothell, WA), a blood vessel image enhancer able to visualize smaller, low-flow vessels and thus possibly the microvascular angiogenesis often associated with cancer, was employed to see if it would improve prostate cancer detection, particularly in patients with a rising serum PSA and prior negative biopsies., Methods: Color Doppler TRUS was performed before and after intravenous injection of 0.05 ml/kg of EchoGen. Random and/or specifically directed sextant TRUS biopsies were performed., Results: Fifteen patients with serum PSA elevations were included in the study. Fourteen had a negative prior biopsy (1-3 x). Prostate cancer was detected in 5 patients. Microvascular patterns were judged abnormal in 8 patients, 2 of which proved malignant, 2 of which were benign, and 1 of which was diagnosed with prostatis. False-negative results were observed in 3 patients, whose positive biopsy sites were from the prostate apex., Conclusions: Following EchoGen administration, prostate blood vessel image enhancement was noted in all patients, and there were no adverse reactions during or after EchoGen administration with the dose employed.

The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.

Patients with growth hormone deficiency (GHD) have traditionally been described as having increased insulin sensitivity with a tendency toward fasting hypoglycemia, at least in children. In other studies, impaired glucose tolerance has been found. To evaluate basal insulin sensitivity, a hyperinsulinemic, normoglycemic clamp was performed with an insulin rate of 40 mU/m2/min after an overnight fast. Fifteen patients (four women and 11 men aged 20 to 62 years) with GHD for at least 1 year were compared with 15 healthy controls matched for sex, age, and body mass index (BMI). Thirteen patients had complete pituitary deficiency and were being treated with conventional hormone replacement therapy. Two men had isolated GHD since childhood. Four men were being treated with bromocriptin. There were no significant differences between fasting blood glucose (4.4 +/- 0.1 v 4.7 +/- 0.2 [mean +/- SEM] mmol/L) or fasting plasma insulin (9.5 +/- 1.4 v 8.8 +/- 1.1 mU/L) in patients and controls, respectively. Fasting free fatty acid (FFA) levels were lower in patients (444 +/- 35 v 796 +/- 94 mumol/L, P < .01). Blood glucose levels during the clamp were similar (4.6 +/- 0.1 v 4.9 +/- 0.1 mmol/L), as were insulin levels (81 +/- 4 v 93 +/- 4 mU/L). A decrease in glucose infusion rate (GIR) was seen during the clamp in GHD subjects (3.9 +/- 0.5 v 9.9 +/- 0.7 mg/kg body weight/min) as compared with controls (P = .001). Even if corrections were made for body fat, there was a significant difference (GIR corrected per lean body mass, 5.8 +/- 0.8 v 13.9 +/- 0.9 mg/kg lean body mass/min, P < .001). The results suggest that adults with GHD are insulin-resistant. Despite this finding, normal fasting plasma insulin levels were seen.

A recent study of 10 men with postpolio syndrome indicated a low secretion of growth hormone (GH) as reflected by serum insulin-like growth factor-I (IGF-1). Therefore, 87 patients were studied, 17 to 71 years after acute poliomyelitis, of whom 65% reported the occurrence of new or increased weakness (ie, during the last 2 years) in muscles previously affected by polio. Serum IGF-1 concentrations in the patients were compared with those found in a reference population comprising 392 randomly selected individuals. No differences from the reference population values were observed. No correlation was found between IGF-1 concentrations and the severity of the original polio affliction, the recovery status, the need for ambulation aids, or the presence of new symptoms. The results do not indicate a need for GH substitution treatment of patients with postpolio syndrome.

GH has multiple effects on growth and metabolism, and these functions are mediated through binding to specific cell surface receptors. The human GH receptor (GHR) exists in two known isoforms; in one form exon 3 is present (GHR3+), and in the other, exon 3 is absent (GHR3-). Recent reports have suggested that the expression of the two isoforms is tissue specific and/or developmentally regulated. We used a reverse transcription-polymerase chain reaction assay to study the expression pattern of the two isoforms in a variety of tissues from normal subjects and patients with acromegaly. In skeletal muscle from both normal subjects and patients with acromegaly, the GHR3+ transcript was expressed, either alone or together with the shorter (GHR3-) transcript. When multiple tissues from six subjects were tested, the expression of the two isoforms varied among subjects, whereas different tissues from the same subject showed the same expression pattern. These results indicate that the expression of the GHR isoforms is not tissue specific. Instead, the expression of the GHR isoforms appears to be specific for each individual, suggesting that it is under the control of factors that affect all tissues in the body.

The aim of this study was to characterize the acute effect of euglycemic (glucose 5.2 +/- 0.6 mmol/l) hyperinsulinemia (mean 118 +/- 32 mU/l) on fibrinolytic variables, free fatty acids (FFA) and counterregulatory hormones. In addition, the effect of chronic treatment with metformin, an oral antidiabetic agent which enhances insulin action, and metoprolol CR, a relatively beta 1-selective adrenergic antagonist, was also evaluated. A randomized, double-blind, placebo-controlled, cross-over study including 18 non-obese men, aged 53 +/- 6 years, was performed. The investigations were performed after each treatment period of 6 weeks in both the postabsorptive state and during a euglycemic, hyperinsulinemic clamp. Compared to the postabsorptive state, plasminogen activator inhibitor (PAI-1) activity and antigen, tissue plasminogen activator (t-PA) antigen and FFA decreased (p < 0.001) after 120 min of euglycemic hyperinsulinemia. In addition, t-PA activity increased (p < 0.01) while blood levels of lipoprotein (a), catecholamines and cortisol remained unchanged. Growth hormone increased during the clamps and this was most pronounced after treatment with metoprolol CR. When the effect of treatment was compared, postabsorptive levels of C-peptide, FFA and t-PA antigen were lower after metformin than after the placebo period (p < 0.05). t-PA antigen also remained lower during the clamp after metformin treatment. No significant effects of metformin or metoprolol CR were seen on insulin-stimulated glucose uptake during the clamps or on postabsorptive levels of counterregulatory hormones, PAI-1 or Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To study the effect of metformin and metoprolol CR on insulin sensitivity, blood lipids, fibrinolytic activity and blood pressure., Design: A double-blind, placebo controlled, triple cross-over study with randomization to either metformin, 850 mg b.i.d., or metoprolol CR 100 mg o.d., or placebo for a period of 18 weeks. The glucose uptake was measured with the euglycaemic clamp technique after every 6 weeks' treatment period. Blood pressure and blood samples were taken every 3rd week., Subjects: Eighteen non-obese men (53 +/- 6 years of age)., Results: Metformin decreased C-peptide (P < 0.02), FFA (P < 0.003), total and low-density lipoprotein cholesterol, tissue plasminogen activator antigen and the urinary potassium excretion (P < 0.05 for all), but not blood pressure compared to placebo. Metoprolol CR reduced diastolic blood pressure and pulse rate; fasting free fatty acids and the urinary potassium increased (P < 0.05 for all). No effect of metformin or metoprolol CR was seen on the glucose disposal rate, blood glucose, plasma insulin, triglycerides, high-density lipoprotein cholesterol, lipoprotein(a), uric acid or plasminogen activator inhibitor 1 activity or antigen. The glucose uptake was not particularly decreased in these subjects., Conclusion: The study shows that metformin has some favourable effects on metabolism and that metoprolol CR is fairly neutral in this regard. The lack of effect of metformin on glucose disposal rate and blood pressure can be explained by the fact that the individuals studied were neither insulin resistant nor hypertensive. The data does not preclude an antihypertensive effect by treating a concomitant insulin resistance.

Hypopituitary patients on routine replacement therapy except growth hormone (GH) have an increased risk of death from cardiovascular diseases compared with healthy subjects. Untreated GH deficiency might explain the premature death from vascular disease. Plasminogen activator inhibitor (PAI-1) activity, fibrinogen, insulin, blood lipid, and blood pressure levels were studied in 20 GH-deficient adults (10 men, 10 women) 50 +/- 11 years old with routine hormone replacement therapy (except GH) and compared with 20 healthy control subjects matched for sex, age, and body mass index. GH-deficient subjects had a higher waist-to-hip circumference ratio (P < .001), serum triglycerides (P < .02), PAI-1 activity (13.2 +/- 10.6 versus 6.8 +/- 4.8 U/mL [P < .05]), and fibrinogen (3.2 +/- 0.7 versus 2.4 +/- 0.6 g/L [P < .001]) and lower blood glucose (P < .05) compared with control subjects. Blood pressure, insulin, and cholesterol levels were similar. The aberrations found in this study might contribute to an increased atherothrombotic propensity and play a role in the pathogenesis of cardiovascular disease.

The aim of this study was to investigate the skeletal muscle sodium/potassium (Na/K) ratio in acromegaly before and 1 year after trans-sphenoidal removal of a growth hormone (GH)-secreting pituitary adenoma. Muscle biopsies were taken and skeletal muscle electrolytes, body composition, glucose, insulin and blood pressure were studied. Fasting blood glucose and plasma insulin levels, but not blood pressure, were higher in acromegalic patients (N = 9) than in controls (N = 6). The skeletal muscle potassium content was higher (p < 0.01) but the sodium content and the Na/K ratio were lower (p < 0.05 and p < 0.001, respectively) in untreated patients with acromegaly as compared to weight-matched healthy controls. Elevated GH, glucose and insulin levels normalized after surgery. Blood pressure remained unchanged. The total body potassium content, the lean body mass and the total body water content decreased and the body fat content increased while the body weight was unchanged. The skeletal muscle potassium content decreased from [medium (range)] 9.8 (9.2-11.5) to 7.7 (5.7-9.5) mmol/100 g wet wt (p < 0.001). The skeletal muscle sodium content increased from 2.8 (2.5-3.9) to 5.1 (4.3-6.7) mmol/100 g wet wt (p < 0.001) and the Na/K ratio increased from 0.28 (0.26-0.38) to 0.56 (0.51-1.18) (p < 0.001) after surgery, which is a higher level than the controls with a Na/K ratio of 0.47 (0.39-0.84) (p < 0.01). These changes seem to be mediated by a decreased GH effect on the Na/K pump after successful trans-sphenoidal surgery in acromegaly.

Objective: To test possible differences between patients with Alzheimer's disease (AD) and patients with other forms of dementia and the healthy population concerning body composition, blood pressure, metabolic data and leukoaraiosis (LA)., Design: Retrospective study on data collected according to a predefined protocol., Setting: A geriatric, neuropsychiatric diagnostic unit., Subjects: Seventy-one consecutive patients with dementia., Main Outcome Measures: Body mass index, blood pressure, metabolism and LA in AD compared to other dementia forms., Results: Mean blood pressure and fasting blood glucose levels were lower in patients with AD, 94 +/- 12 mmHg and 4.3 +/- 0.5 mmol l-1, compared to patients with unspecified dementia (NUD), 100 +/- 10 mmHg and 5.5 +/- 2.5 mmol l-1 (P < 0.05) and vascular dementia (VAD), 114 +/- 12 mmHg and 5.6 +/- 1.6 mmol l-1 (P < 0.001) and the age-matched healthy population. Body mass index, serum cholesterol and cortisol were similar in all groups of dementia patients whereas triglycerides were highest in the VAD group. No cases of diabetes or treatment for hypertension were found in the AD group while the prevalence was 21% and 36% for diabetes in the NUD and VAD groups and 8% in the population from the same region. There were 16% with antihypertensive treatment in dementia NUD, 50% in VAD, and 30% in the general population. Treated or newly detected hypothyreosis was present in 11% of the AD patients, none in the other dementia groups and 2% in the general population. Smoking was least common in AD. Degree of LA correlated with blood pressure and blood glucose levels., Conclusions: AD was clearly different to other dementia patients. They had lower blood pressure, blood glucose and higher prevalence of hypothyreosis than the healthy, age-matched population. These findings may indicate that AD could be a hypometabolic disorder.

The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp.

Insulin resistance and hyperinsulinaemia may play an important role in both the development of hypertension and its accompanying metabolic aberrations. In order to investigate this possibility, nine non-obese, non-diabetic, non-smoking, middle-aged men with untreated hypertension were treated with metformin 850 mg b.i.d. for 6 weeks as a pilot study and within-patient comparison. Metformin decreased total and LDL-cholesterol (P less than 0.01), triglyceride (P less than 0.01), fasting plasma insulin (P less than 0.01) and C-peptide levels (P less than 0.02). Glucose disposal, an indicator of insulin action measured by means of the euglycaemic clamp technique, increased (P less than 0.001). Tissue plasminogen activator (t-PA) activity increased (P less than 0.02), and t-PA antigen decreased (P less than 0.01), whereas plasminogen activator inhibitor (PAI-1) and fibrinogen were unaffected by metformin treatment. Body weight remained unchanged. Withdrawal of metformin was associated with the return of both blood pressure and metabolism towards the initial levels. In conclusion, metformin treatment increased insulin action, lowered blood pressure, improved the metabolic risk factor profile and tended to increase the fibrinolytic activity in these mildly hypertensive subjects. These results support the view that insulin resistance plays a role in hypertension, and may open up a new field for the alleviation of abnormalities associated with cardiovascular disease.

Several previous studies have suggested that hypertension is associated with altered sodium transport across the cell membrane. The aim of the present study was to study the skeletal muscle Na:K ratio in relation to blood pressure and glucose tolerance in obese and non-obese men. Muscle biopsies were taken from the femoral vastus lateralis muscle in men aged 52 +/- 5 years and the electrolytes were analyzed. Ten obese men with impaired glucose tolerance and hypertension, 10 obese normotensive controls, 10 lean men with hypertension and 10 lean normotensive controls participated in the study. Higher insulin levels were found in both hypertensive groups compared with the respective normotensive groups. Increased muscle Na:K ratio was found in obesity (P less than 0.01) and this was further enhanced when combined with hypertension and impaired glucose tolerance (P less than 0.001). However, hypertension in lean individuals was not associated with an increased muscle Na:K ratio. These data suggest that the increased muscle Na:K ratio in obese subjects and those with impaired glucose tolerance is not solely due to insulin resistance and hyperinsulinemia. Furthermore, the data clearly suggest that there is no important general perturbation of the Na-K pump in hypertension per se.

Hypertension is related to several conditions with abnormalities in carbohydrate and lipid metabolism, such as obesity and impaired glucose tolerance. However, perturbed metabolism is also seen in non-obese hypertensive individuals. In addition, hypertension is linked to impaired fibrinolysis and elevated levels of the plasminogen activator inhibitor of endothelial type (PAI-1). Insulin resistance and hyperinsulinaemia in essential hypertension may be an important cause of these metabolic and fibrinolytic abnormalities. Whether hyperinsulinaemia is the cause of hypertension is currently unknown. However, it is clear that the relationship between hypertension and insulin is complex, and further studies are required to clarify this association. Based on the evidence states, it is suggested that insulin resistance and hyperinsulinaemia play a role in hypertension. However, it is also clear that hyperinsulinaemia occurs in the absence of hypertension, which suggests that other factors, such as genetic susceptibility, may be important.

Recent epidemiologic studies have shown that abdominal obesity, characterized by a high waist to hip circumference ratio (WHR), is associated with increased cardiovascular morbidity and mortality. The present study examines components of the fibrinolytic system in obese and lean middle-aged women with a high and low WHR. Ten women in each group were carefully matched with respect to age, body weight, lean body mass, and body fat. Fibrinogen and endothelial type of plasminogen activator inhibitor -1 (PAI-1) were significantly elevated in the obese women with a high WHR compared with the obese women with a low WHR or with both groups of lean women. In addition, obese women with a high WHR exhibited a greater metabolic risk profile (elevated glucose, insulin, and triglyceride levels). When all subjects were pooled for the analyses, both fibrinogen and PAI-1 levels correlated positively with glucose and insulin levels. PAI-1 was also negatively related to degree of insulin sensitivity measured with the euglycemic clamp technique. In the obese groups, WHR but not body mass index (BMI), correlated with PAI-1 levels. No such correlations were seen in the lean groups. In conclusion, the data show that a high WHR in obese, but not lean middle-aged women, is associated with an impaired fibrinolytic activity. This perturbation becomes enhanced when it is associated with hyperinsulinemia and insulin resistance, which is a typical feature of abdominal obesity.

The relationship between hypertension, glucose metabolism, fibrinogen and plasminogen activator inhibitor of endothelial cell type (PAI-1) was studied under conditions in which the influence of obesity and adipose tissue distribution (waist/hip ratio) were controlled. Twenty-two non-obese, middle-aged men with normal blood pressure (n = 11) and untreated mild hypertension (n = 11), respectively, participated in the study. Cholesterol, triglyceride and insulin levels were higher in hypertensive men than in the control group. Glucose disposal was studied as an indicator of insulin sensitivity using the euglycaemic clamp technique. The insulin effect tended to be less marked in men with hypertension. PAI-1 was higher in hypertensive men compared to the controls. A strong positive correlation was observed between PAI-1 and insulin levels as well as blood pressure. PAI-1 and fibrinogen levels correlated negatively with the rate of glucose disposal. Thus, even in these non-obese and mildly hypertensive individuals, an enhanced metabolic risk factor profile for cardiovascular disease was found. The metabolic aberrations were related to elevated fibrinogen and PAI-1 levels which, in turn, increase the risk of thrombus formation.

The effect of body weight on total body potassium, skeletal muscle electrolytes and fat content was studied in seven lean and seven obese middle-aged men and seven lean and eight obese middle-aged women. Total body potassium and total body fat increased with body weight (p less than 0.01 and less than 0.05 for men, and p less than 0.05 and p less than 0.001 for women, respectively). So did muscle fat in men (p less than 0.01), while muscle tissue potassium was decreased in both obese men (p less than 0.001) and obese women (p less than 0.05). The skeletal muscle Na/K-ratio tended to be higher in obese men (p less than 0.1) but was not related to body weight in women. Skeletal muscle magnesium was higher (p less than 0.01) in obese men than in lean men. No differences between lean and obese women were found. Obese men had higher diastolic blood pressure (p less than 0.05) than lean men, while there was no difference between obese and lean women. Compared with lean subjects, obese subjects thus had lower relative skeletal muscle mass and men, especially, had more fat and less potassium in the skeletal muscle.

Obese people with a high waist/hip ratio (W/H ratio) have an increased risk for cardiovascular disease. The present study was designed to separately analyze the importance of obesity and the regional fat distribution for the metabolic risk factors. Blood pressure, glucose tolerance, insulin, and plasma lipid levels were studied in lean and obese postmenopausal women with a high or low W/H ratio. The individuals within each group were carefully matched for age, lean body mass, and body fat. The risk factors associated with a high W/H ratio (elevated blood pressure, blood lipids, and glucose levels) were found in the obese but not in the lean women. Furthermore, lean women with a high W/H ratio tended to have a lower metabolic risk factor profile than obese women with a low W/H ratio. These findings document the importance of obesity in expressing the metabolic risk factors for cardiovascular disease associated with a high W/H ratio.

The effects of obesity, weight reduction, and physical condition on the concentrations of glucose-6-phosphate (G-6-P) and glycogen, and the activities of glycogen synthase (GS) and lactate dehydrogenase (LD) were determined in resting vastus or gastrocnemius muscles of 40 healthy subjects. In obese women the activity of GS was 50% (P less than 0.05) lower than in lean women with similar levels of glycogen and G-6-P, whereas no difference was found in the activity of LD. Calorie restriction induced a 4.5% (P less than 0.05) decrease in body weight from 82.5 kg corresponding to a 3.2% (P less than 0.05) decrease in body mass index from 30.9 kg m-2. The total and fractional activities of glycogen synthase were increased by 50% (P less than 0.05), whereas muscle glycogen content was reduced by 40% (P less than 0.05). The G-6-P concentration and the activity of LD remained unchanged. In well-trained young men the concentrations of G-6-P and glycogen were, respectively, 250% (P less than 0.05) and 50% (P less than 0.05) higher than in non-trained. The fractional and total activities of GS were 90% (P less than 0.05) and 50% (P less than 0.05) higher, respectively, and the total activity of LD was only half (P less than 0.05) that of non-trained subjects. In conclusion, physical training enhances the activity of GS, despite a concomitantly increased glycogen content, and thus seems to exert a more efficient stimulus on glycogen synthase than weight reduction. It is indicated that physical training may provide a clinically important contribution to blood glucose reduction in hyperglycaemic conditions.

Body composition calculated from total body potassium and skeletal muscle potassium were studied in middle-aged obese men and women with normal and impaired glucose tolerance as well as Type II diabetes before and after advice on calorie reduction during twelve months. The subjects were compared with healthy lean men and women. Mean weight loss was 6.6 kg (P less than 0.05). Lean body mass and body fat decreased 2.0 kg (P less than 0.05) and 4.6 kg (P less than 0.05), respectively. Total body potassium decreased by a mean of 146 +/- 49 mmol (P less than 0.01). Obese men with Type II diabetes and impaired glucose tolerance had lower total body potassium and muscle potassium levels than obese healthy men. After dieting, the obese men and women increased their muscle potassium levels with a mean of 2.8 mmol/100 fat-free dry weight to 42.6 +/- 2.6 mmol/100 g fat-free dry weight (P less than 0.05), but they were still below the levels of the lean controls, 44.4 +/- 1.3 MMOL/100 g fat-free dry weight, (P less than 0.01). Increase in skeletal muscle potassium was correlated to decrease in body weight, r = 0.55 (P less than 0.01) and to decrease in fasting blood glucose, r = 0.42 (P less than 0.05).