Transcutaneous Electrical Nerve Stimulation Improves Exercise Tolerance in Healthy Subjects.

Transcutaneous electrical nerve stimulation (TENS) increases peripheral blood flow by attenuation of the muscle metaboreflex, improving oxygen supply to working muscles. We tested the hypothesis that application of TENS at ganglion improves exercise performance. 11 subjects underwent constant-work rate tests (CWR) to the limit of tolerance (Tlim) while receiving TENS or placebo. Oxygen uptake (V.O2), carbon dioxide (V.CO2), minute ventilation (V.E), ventilatory equivalent (V.E/V.CO2), heart rate (HR) and oxygen pulse (V.O2/HR) were analyzed at isotime separated by percentile and Tlim. V.O2 was lower and V.CO2 was higher at 100% of isotime during TENS, while there were no differences in V.E and V.E/V.CO2. HR was lower during exercise with TENS, and V.O2/HR increased at peak exercise (17.96±1.9 vs. 20.38±1 ml/min/bpm, P<0.05). TENS increased mechanical efficiency at isotime and Tlim (4.10±0.50 vs. 3.39±0.52%, P<0.05 and 3.95±0.67 vs. 3.77±0.45%, P<0.05) and exercise tolerance compared to P-TENS (390±41 vs. 321±41 s; P<0.05). Our data shows that the application of TENS can potentially increase exercise tolerance and oxygen supply in healthy subjects.

Prescription of oral antidiabetic drugs in K/DIGO chronic kidney disease stage 3 and 4: a single centre report.

AIM: Evaluation of chronic kidney disease (CKD) is essential in order to prescribe properly oral antidiabetic drugs (OADs). The aim of our study was to report hypoglycemic drugs prescription to CKD in a cohort of type 2 diabetes mellitus (DM) outpatients. METHODS: This survey included 1686 outpatients with type 2 DM treated with OADs who were not taking insulin evaluated by a team of diabetologists. Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula and subjects were classified in the K/DIGO stages. Main clinical parameters were also evaluated. RESULTS: Patients were aged 68±10 years, 57.1% were males, Body Mass Index was 30±5 kg/m2, glycated hemoglobin 8±1%, systolic and diastolic blood pressure values were 138±15/80±9 mmHg. Serum creatinine was 1.03±0.35 mg/dL and GFR 71±21 mL/min/1.73 m2. In 504 patients (30%) GFR was lower than 60 mL/min/1.73 m2. The different treatment groups had different GFR and hypoglycaemic drugs were prescribed differently in the different K/DIGO stages. The majority of subjects in stage 3A and 3B were treated with repaglinide, however a significant percentage of them were treated with metformin and sulfonylureas. Nearly half of subjects with CKD stage 4 were treated with metformin and sulfonylureas. CONCLUSION: In this report we found that nearly one third of patients with type DM 2 had CKD and in a significant percentage of them OADs were prescribed even if they were in K/DIGO CKD stage 3 and 4.

The estimation of glomerular filtration rate in type 2 diabetic patients may depend on the equation used.

BACKGROUND: The aim of this study was to compare the estimation of glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM) outpatients. PATIENTS AND METHODS: The study included 1686 subjects, aged 68±10 years. GFR was evaluated with five different equations: GFRMDRD186, GFRMDRD175, GFRCKD-EPI, GFRMAYO, GFRC-G. RESULTS: GFR was lower than 60 ml min-1 kg-1 in 456 patients (27%) by GFRMDRD186, in 531 (31.5%) by GFRMDRD175, in 504 (30%) by GFRCKD-EPI, in 433 (26%) by GFRC-G, and in 255 (15%) by GFRMAYO. The mean differences in measuring GFR with the different formulae ranged from 1.03±6.20 to -14.5±11.9 ml min-1 1.73 m2-1. CONCLUSIONS: The evaluation of GFR with different formulae in type 2 DM patients may identify different chronic kidney disease (CKD) stages. Physicians could take advantage by the knowledge of the formula used for evaluation of renal function, for a better interpretation of values and a more appropriate use in the everyday clinical practice.

Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome.

Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.

Weight cycling in treatment-seeking obese persons: data from the QUOVADIS study.

OBJECTIVE: To determine parameters of weight history useful for the assessment of weight cycling and their association with psychological distress and binge eating. DESIGN: Cross-sectional. SUBJECTS: A total of 1889 treatment-seeking obese subjects, enrolled by 25 Italian centers (78% female subject), aged 20-65 y (median 45); 1691 reported previous efforts to lose weight (median age of first dieting, 30 y). MEASUREMENTS: The number of yearly attempts to lose weight, weight gain since age 20 y, cumulative weight loss and gain were checked by a predefined structured interview. Psychological distress was tested by means of Symptom Check-List 90 (SCL-90), Binge Eating Scale (BES) and Three Factor Eating Questionnaire (TFEQ). RESULTS: Differences in anthropometric, clinical and psychological parameters were observed in relation to previous attempts to lose weight. Patients in the upper quartile of parameters of weight history were considered weight cyclers. In multivariate logistic regression analysis, after correction for age, sex and BMI, a high BES score was the only factor systematically associated with a high frequency of dieting (OR, 1.70; 95% confidence interval, 1.22-2.36; P=0.022), with higher cumulative weight loss (1.42; 1.12-1.80; P=0.003) and cumulative weight gain (1.38; 1.06-1.79; P=0.017). However, the sensitivity, specificity and positive predictive value of a high BES score were very low to detect cyclers. Weight cycling did not carry a higher risk of complicating diseases. CONCLUSIONS: Weight cycling is associated with psychological distress, and binge eating independently increases the risk, but cannot be used to predict cycling. Also, obese patients who do not experience overeating as a loss of control discontinue treatment or regain weight following therapy.

Monitoring O3 with solar-blind Raman lidars.

The benefits of retrieving ozone concentration profiles by a use of a single Raman signal rather than the Raman differential absorption lidar (DIAL) technique are investigated by numerical simulations applied either to KrF- (248 nm) or to quadrupled Nd:YAG- (266 nm) based Raman lidars, which are used for both daytime and nighttime monitoring of the tropospheric water-vapor mixing ratio. It is demonstrated that ozone concentration profiles of adequate accuracy and spatial and temporal resolution can be retrieved under low aerosol loading by a single Raman lidar because of the large value of the ozone absorption cross section both at 248 nm and at 266 nm. Then experimental measurements of Raman signals provided by the KrF-based lidar operating at the University of Lecce (40 degrees 20'N, 18 degrees 6'E) are used to retrieve ozone concentration profiles by use of the Raman DIAL technique and the nitrogen Raman signal.

Water-vapor mixing-ratio measurements in the solar-blind region.

It is shown that, under clear sky conditions, water-vapor mixing-ratio measurements by solar-blind Raman lidars can be improved if the differential transmissivity is calculated by use of a single Raman signal instead of the usual Raman differential absorption lidar method, which allows one to exploit the large absorption cross section of ozone in this spectral region. We present a discussion of statistical and systematic errors in both methods and show the results of a numerical simulation.

Therapeutic benefit of benfluorex in type II diabetic patients treated with sulfonylureas.

The objective of this study was to evaluate the effect of benfluorex in type II diabetic patients already treated with sulfonylureas (SU) in a randomized placebo-controlled trial. After a 4-week placebo run-in, 68 patients (49 men and 19 women; age range 40-70 years; known duration of diabetes 0.5-19 years) were randomized to double-blind 12-week treatment with benfluorex (B) or placebo (P). Primary end points were HbA1c and fasting blood glucose (FBG). Secondary end points were glucose tolerance (meal test over 120 min), plasma insulin, C-peptide, and lipid profile. Results were analyzed using both intention-to-treat analysis (ITT) in patients completing at least one treatment visit and per protocol analysis in those completing the whole study. There were no baseline differences between the two groups in any study parameter. Fifty-eight patients completed the study (28 B, 30 P), and 66 patients (33 B, 33 P) were eligible for ITT analysis. Over the 12-week treatment period, FBG decreased by 14.9% in the B group (-1.39 mmol/L, p < 0.001), and 3.2% in the P group (-0.28 mmol/L, NS) according to the ITT analysis and by 17.4% (p < 0.001) and 3.8% (NS), respectively, in the per protocol analysis. The difference in FBG outcome between the two groups was significant (p = 0.009 and p = 0.004, respectively). In patients completing the study, mean HbA1c decreased in the B group (-0.66%, p = 0.005) and remained stable in the P group (+0.14%, NS). HbA1c outcome differed between the two groups (p = 0.007). The decrease in AUCglucose was greater in the B group than in the P group (-210 +/- 220 versus -60 +/- 270 mmol/L x 120 min, p = 0.026). Plasma insulin and C-peptide changes did not differ between the two groups. Low-density lipoprotein (LDL) cholesterol decreased in B patients and was stable in P patients (-0.43 versus -0.05 mmol/L, p = 0.026). Of the 68 randomized patients, six on B and four on P reported at least one adverse event, causing dropout in five and two patients, respectively. In conclusion, benfluorex is an effective agent for combination therapy in type II diabetic patients poorly controlled on SUs alone.

The importance of the highest normokalemia in the treatment of early hepatic encephalopathy.

An inverse relation is known to link blood potassium with renal synthesis and the release of ammonia. Given the liability of hyperammonemia for precipitating hepatic encephalopathy (HE), 28 patients affected by stage I HE were equally divided into two groups and maintained up to their death at the highest (5.4-5.5 mEq/l) or the lowest (3.5-3.6 mEq/l) normokalemia levels. When compared with the lowest normokalemia group, the highest one showed an early, albeit transient, improvement in the mental state (as assessed by both EEG and psychiatric investigations) and to a lesser extent in hepatic functions (as assessed by the variations in serum bilirubin, GPT, GGT and plasma prothrombin time). In the highest normokalemia group the survival was also prolonged. The cause of this improvement may be related to the induced decrease in blood pH, the consequent depression of renal ammoniagenesis and the rise in the arterial and urine NH+4/NH3 ratios. These factors reduce the entry of ammonia into the cells and enhance the urinary excretion of this metabolite, respectively.

Risk factors associated with persistence of glucose intolerance one year after gestational diabetes.

One hundred and fourteen women, 89 with previous gestational diabetes and 25 who showed a normal glucose tolerance during pregnancy were retested by OGTT one year postpartum. Gestational diabetics were divided into two groups according to the severity of glucose intolerance. 97.6% of mild gestational diabetics and 79.2% of severe cases returned to normality postpartum. A different behaviour of these groups was shown by comparing OGTT areas before and after delivery. Body Mass Index and the degree of severity of glucose intolerance were shown to be predictive for the persistence of the abnormality postpartum. Follow-up for three to four years was continued in 8 cases of previous severe gestational diabetes. In seven of them a glucose intolerance appeared again during the follow-up after the temporary improvement one year after delivery.

Glycosylated hemoglobin (HbA1) assay as a test for detection and surveillance of gestational diabetes. A reappraisal.

Total glycosylated hemoglobin (HbA1) levels were measured in 96 gestational diabetics and 139 normal pregnant women in order to assess their usefulness in detection and monitoring of gestational diabetes. Different, although not significant, behaviour of HbA1 values was found in gestational diabetics and controls throughout pregnancy. Significantly higher (p less than 0.005) HbA1 values were found in gestational diabetics between the 24th and the 32nd week of gestation. In spite of this finding a low sensitivity in detecting gestational diabetes was confirmed. HbA1 values and OGTT parameters did not correlate. Delivery of a large-for-date (LGA) baby was not associated with higher HbA1 levels. Overlapping HbA1 levels were found in gestational diabetics and normal pregnant women. This study confirm the low predictive value of HbA1 assay in gestational diabetes.

A double-blind controlled study to compare the efficacy of an antacid plus oxethazaine with that of an antacid alone in the treatment of pain due to gastric or duodenal ulceration.

A double-blind study was carried out in 40 patients with typical ulcer pain and suffering from gastric or duodenal ulcer to compare the pain-relieving efficacy of oxethazaine/magnesium and aluminium hydroxide mixture with that of the antacid combination alone. Patients took 8 ml doses of either treatment when necessary over a period of 4 weeks. Both treatment regimens were equally effective in reducing the painful symptoms of peptic ulceration, but the total volume of medication required to achieve adequate symptomatic relief was less in patients taking antacid plus oxethazaine than in patients taking antacid alone. It is suggested that the combination of oxethazaine plus antacids, therefore, is to be preferred, because, by allowing a reduction in the intake of antacid, the risk of side-effects due to antacid therapy is thereby reduced.

Orgotein as a radioprotector in normal tissues. Experiments on mouse skin and a murine adenocarcinoma.

The effects of Orgotein (a superoxide dismutase) on the radiation response of normal and malignant murine tissue in vivo were evaluated. The observations were made on the mouse hind leg bearing, in some cases, an adenocarcinoma. The following irradiation protocols were tested: 1) single dose (e.g., 35 and 53 Gy), 2) conventional fractionation (3 Gy/day, 5 days a week) and 3) multiple fractions per day (2 X 3 Gy/day, 3 h fractionation interval, 5 days a week). Radiation was either delivered alone or preceded by a subcutaneous injection of 20, 100 or 400 mg/kg Orgotein administered 1 or 2 h before the beginning of irradiation. No effects of Orgotein on tumor radiation response were detected. A protective effect on normal tissue was observed when radiation was delivered according to aggressive protocols and a relatively high dosage of Orgotein was administered. Furthermore, an accelerated trend of recovery of normal tissue was observed.

Induction of ovulation with purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome.

Purified urinary follicle-stimulating hormone was used to induce ovulation in 18 patients with polycystic ovarian syndrome. Each ampule contained 75 IU of follicle-stimulating hormone and less than 0.11 IU of luteinizing hormone. Initial doses were 150 to 225 IU/day, later increased to a maximum of 375 IU, according to daily clinical controls and estradiol values. After 12 to 16 days, follicle-stimulating hormone treatment was suspended. Within 36 to 48 hours each patient received 5000 or 10,000 IU of human chorionic gonadotropin, rarely more. Ovulation occurred in 39 of 43 treatment cycles and hyperstimulation in nine. Seven patients had normal pregnancies with viable fetuses, including one pair of twins. Two had abortions. Analysis of the endocrine situation during therapy does not permit either pregnancy or hyperstimulation to be predicted. However, hyperstimulation is frequently accompanied by endogenous luteinizing hormone peaks and greater estradiol increases during the final phase of induction. Purified follicle-stimulating hormone has thus demonstrated its validity in inducing ovulation in patients with polycystic ovarian syndrome, apparently with equal or lower risks of hyperstimulation than with other gonadotropin preparations.

Pavel's "dynamic screening" for diabetes type 2: 14 years results in a district of northern Italy.

The AA. report the results of 14 years' screening for diabetes type 2 in their Health District (Emilia Romagna, North Italy), according to Pavel's method, for early diagnosis of clinical diabetes and impaired glucose tolerance (IGT). The AA. found in a first screening 1.03% of clinical diabetes and 2.65% of IGT cases in the population examined (200,000 subjects). Statistically significant correlations existed in relation to the various risk factors (hereditary factors, obesity, fetal macrosomia, job). The follow-up after 6 years for IGT subjects showed a 25.5% return to normal oral glucose tolerance test (OGTT) values, 21.7% improvement, 19% unchanged, 33.8% impairment. There was a correlation between these results and life-style (diet, physical exercise, weight loss). Fourteen years after these screening, a 2.7% negative incidence was observed for diabetes type 2 in this Health District.