Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

Plasma and liver cholesterol concentrations in mice fed semipurified diets differing in the amount of cholesterol and type of fat

Male and female mice of two inbred strains were fed semipurified diets with or without added cholesterol (1%, w/w) containing 18% by weight of either coconut fat or corn oil. After 28 days coconut fat had produced higher concentrations of plasma cholesterol than corn oil in almost all groups, irrespective of whether the diets contained cholesterol or were cholesterol-free. On the cholesterol-free diets, the type of fat did not influence the concentration of liver cholesterol. Dietary cholesterol caused a marked increase in liver cholesterol, the magnitude of the effect being dependent on the strain of mice and being greater in females than males. In all groups fed cholesterol corn oil caused significantly higher concentrations of liver cholesterol than coconut fat.     

Transient lowering of plasma vitamin B12 concentrations in Ouessant sheep fed on a potassium-rich ration.

The hypothesis tested was that a high intake of potassium (K) interferes with cobalt (Co)-vitamin B12 metabolism in ruminants. Ouessant sheep were fed either a low- (8 g K/kg dry matter) or high-K diet (43 g K/kg dry matter) with an adequate amount of Co (124 micrograms Co/kg dry matter). Plasma vitamin B12 concentrations were measured. Sheep fed a low-K diet, but containing only 70 micrograms Co/kg dry matter, served as positive controls. Feeding the low-Co ration produced a significant decrease in plasma vitamin B12 concentrations. The high- versus low-K ration induced a significant decrease in plasma vitamin B12 during the first 6 weeks, but thereafter the values in the high-K group rose to those seen in the low-K group. The mechanism by which dietary K may interact with Co-vitamin B12 metabolism in sheep is unknown.     

Nitrous oxide exposure in the operating room

One-hundred and eight-five pairs of gas samples were collected from inspired gas (10 cm behind the head at nose level) and end-tidal gas of persons administering anesthesia in 3 operating rooms during daily routine anesthesia. Mean operating-room N2O concentrations from 22 to 144 ppm (volume/volume [V/V]) were measured by gas chromatography, and large moment-to-moment variations (temporal gradients) were seen in individual operating rooms. Mean end-tidal N2O concentrations from 51 to 114 ppm (V/V) were observed. There were low correlations between inspired and end-tidal N2O concentrations (r values as low as r = 0.35). This poor relationship is presumably due to spatial and temporal gradients of N2O in the operating rooms. We conclude that the temporal and spatial gradients in N2O concentrations within active operating rooms are sufficiently large to invalidate estimation of exposure of anesthetic personnel to N2O from "spot" or "grab" samples collected in the breathing area.     

Endoscopic Duodenal–Jejunal Bypass Liner Rapidly Improves Type 2 Diabetes

Background

Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal–jejunal bypass liner (DJBL).

Methods

Seventeen obese patients (BMI 30–50 kg/m²) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA_1c and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment.

Results

At 24 weeks after implantation, patients had lost 12.7?±?1.3 kg (p?<?0.01), while HbA_1c had improved from 8.4?±?0.2 to 7.0?±?0.2 % (p?<?0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6?±?0.5 vs. 9.0?±?0.5 vs. 8.6?±?0.5 mmol/L and 1,999?±?85 vs. 1,536?±?51 vs. 1,538?±?72 mmol/L/min, both p?<?0.01). In parallel, the glucagon response decreased (23,762?±?4,732 vs. 15,989?±?3,193 vs. 13,1207?±?1,946 pg/mL/min, p?<?0.05) and the GLP-1 response increased (4,440?±?249 vs. 6,407?±?480 vs. 6,008?±?429 pmol/L/min, p?<?0.01). The GIP response was decreased at week 24 (baseline—115,272?±?10,971 vs. week 24—88,499?±?10,971 pg/mL/min, p?<?0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation.

Conclusions

The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones.     

Reproducibility of the variations between humans in the response of serum cholesterol to cessation of egg consumption

To find out whether the variable response of serum cholesterol levels to changes in cholesterol intake in man is due to constitutional differences in responsiveness, we have reinvestigated in 1982 34 healthy men and women, who habitually consumed at least 1 egg/day and had participated in a trial in 1976. Serum cholesterol was measured on the habitual diet (about 800 mg cholesterol/day), and after 3 weeks during which no eggs or egg-containing products were consumed (about 300 mg cholesterol/day). Serum cholesterol decreased by 0.16 +/- 0.42 mmol/1 (6 +/- 16 mg/dl) in 1976 and by 0.31 +/- 0.35 mmol/l (12 +/- 14 mg/dl) in 1982 (mean +/- SD). Individual responses varied from -1.0 to +0.5 mmol/l (-39 to +19 mg/dl). The correlation between the responses in 1976 and 1982 was r = 0.32 (P less than 0.05). The decrease in serum cholesterol was most pronounced for subjects with a low body mass index and a high level of HDL-cholesterol. In men, the increase in serum cholesterol with age was correlated with the mean decrease in the trials (r = 0.42, n = 16, P = 0.11). In a controlled trial, 4 hypo- and 2 hyperresponders were given 11 mg cholesterol/MJ (11 mg/240 kcal; 116 mg/day) for 4 weeks followed by 72 mg/MJ for another 4 weeks; all other nutrients were kept constant. Almost all food was supplied and intakes were rigidly controlled. The 2 hyperresponders and 3 of the 4 hyporesponders were also hyper- and hyporesponsive under the controlled conditions. We conclude that part of the cholesterolemic response to dietary cholesterol in man is individually determined and stable for at least 6 years.     

Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study

Background  

Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly.     

The decrease in body fat in mice fed conjugated linoleic acid is due to increases in energy expenditure and energy loss in the excreta

We carried out energy balance studies in four groups of young, growing, 5-wk-old Balb-C mice (n = 12/group) that were either food restricted or nonrestricted and fed high fat diets (38 energy%) with or without 0.93 g/100 g conjugated linoleic acid (CLA) for 39 d. The energy in carcasses, excreta and food was measured in a bomb calorimeter. CLA lowered the percentage of the energy intake that was stored in the body from 1.9 +/- 0.8 to -2.3 +/- 0.7% (mean +/- SD, P < 0.05) in the nonrestricted mice and from 1.4 +/- 1.3 to -2.9 +/- 0.7% (P < 0.05) in the restricted mice. Thus, the CLA-treated mice had a net loss of body energy. The percentage of the energy intake eliminated in the excreta increased from 7.6 +/- 0.9% in controls to 8.7 +/- 1.0% (P < 0.05) in the CLA-treated mice that were nonrestricted and from 7.3 +/- 0.8 to 8.4 +/- 0.6 (P < 0.05) in the restricted mice. The amount of energy ingested minus the amount retained in carcasses and excreta equals the energy expenditure. The percentage of the energy intake that was expended as heat increased from 90.5 +/- 1.2 in controls to 93.6 +/- 1.5% (P < 0.05) in the CLA-treated nonrestricted mice and from 91.3 +/- 1.5 to 94.5 +/- 1.0% (P < 0.05) in the restricted mice. The lower energy storage in the CLA-fed mice was accounted for by an increase in the energy expenditure (74%) and by an increase in energy lost in the excreta (26%). Feeding CLA also increased liver weight, which may warrant further studies on the safety of CLA.