Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish Hip Fracture Study Group

OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.     

Neuronal laterality in Parkinson''s disease with unilateral symptom by in vivo 1H magnetic resonance spectroscopy

PURPOSE: The aim of the present study was to investigate carcinoembryonic antigen (CEA), CA19.9, and CA72.4 in the serum and gastric juice of patients with gastric cancer. METHODS: Serum and gastric juice tumor markers CEA, CA19.9, and CA72.4 were measured in 59 patients who had gastric adenocarcinomas and were undergoing curative gastrectomy. The same markers were measured in 47 patients with benign gastric disorders and in 40 healthy subjects. The correlation between the serum and gastric juice levels of tumor markers and several clinicopathological factors were evaluated by univariate analysis. The significance of the tumor markers as prognostic factors was assessed both by univariate and multivariate analysis. RESULTS: The positivity rates of serum CEA, CA19.9, and CA72.4 were 57.6%, 38.9%, and 18.6% respectively. The positivity rates of gastric juice CEA, CA19.9, and CA72.4 were 62.7%, 30.5%, and 23.7% respectively. The combination of serum and gastric juice markers gave a positivity of 81.3%. There was no correlation between serum and gastric juice level of each tumor marker. Positivity of gastric juice markers did not correlate with prognosis. A significant difference in prognosis was observed between patients positive and negative for serum CEA and CA19.9. Multivariate analysis also revealed that serum CEA and CA19.9 levels were independent prognostic factors. CONCLUSIONS: Levels of both serum and gastric juice tumor markers continue to have only limited diagnostic usefulness in gastric cancer patients. CEA and CA19.9 in the preoperative sera are good prognostic factors, whereas the presence of tumor markers in the gastric juice does not play any prognostic role.     

An analysis of signal-to-noise ratio and design parameters of aterahertz optical asymmetric demultiplexer

Analysis of the signal-to-noise ratio (SNR) as a function of the component parameters in a terahertz optical asymmetric demultiplexer (TOAD) can help optimize its performance as a demultiplexer or as a router in an optical time division multiplexed network. The analysis presented here accounts for crosstalk due to deviation from a perfect 3 dB splitting ratio in the TOAD's 2×2 coupler, and the degradation of SNR due to fluctuations in the control pulse energy. The spontaneous emission noise output of the semiconductor optical amplifier (SOA) contained in the TOAD is simulated under different degrees of saturation. The analysis indicates that leakage due to the asymmetric placement of the SOA contributes significantly to the crosstalk. To achieve a SNR of 21.5 dB or higher in a 100 Gb/s system, one must use a 2×2 coupler that deviates less than 1% from a perfect 3 dB splitting ratio. Also, control pulse energy fluctuations must be less than 10% for a 20-GHz bandwidth electronic receiver. Novel crosstalk-free designs are proposed and analyzed which meet the stringent requirements of current TOAD devices. A significant enhancement in SNR is predicted when the SOA is operated near the optimal saturation point     

Lysosomal enzyme and inhibitor levels in the human trabecular meshwork

PURPOSE: To examine in the human trabecular meshwork lysosomal enzymes and one inhibitor of serine proteases that actively participate in the degradation of macromolecules into low molecular weight constituents. METHODS: Using an avidin-biotin-peroxidase technique, lysosomal proteases and alpha 1-proteinase inhibitor were examined in the trabecular meshwork of 23 human eyes with donor ages ranging from 2 to 90 years. These eyes were categorized into three age groups (< or = 20, 21 to 49, and > or = 50 years). Histochemical staining for lysosomal hydrolases was also performed on frozen sections of 20 human eyes. The staining was analyzed by an image analyzer and the levels of lysosomal proteases were further measured by biochemical assays. RESULTS: The trabecular meshwork from all the eyes stained intensely against antibodies to cathepsins B and G and alpha 1-proteinase inhibitor. The staining for elastase was weaker but evident. Image analyses revealed that the staining intensity for each protease or inhibitor was similar in all age groups. The staining in the uveal meshwork appeared to be the strongest among all the trabecular meshwork regions. Biochemical assays of tissue extracts confirmed that the enzyme and inhibitor levels were comparable among the three donor age groups. Activities of two lysosomal hydrolases, acid phosphatase and acid esterase, were also found in trabecular meshwork cells of 20 eyes. No apparent difference in enzyme activities was found with increasing age, and variation related to region was not observed. CONCLUSIONS: This study demonstrated the age-independent distribution of a variety of lysosomal enzymes and a protease inhibitor in the human trabecular meshwork. The presence of these proteins suggests a possible role in the metabolic operation of the trabecular meshwork.     

Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. RESULTS: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P <.001), but total REE did not change. CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS.     

Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage

1. Intracerebroventricular (i.c.v.) injection of choline (25-150 micrograms) increased blood pressure in rats made acutely hypotensive by haemorrhage. Intraperitoneal administration of choline (60 mg kg-1) also increased blood pressure, but to a lesser extent. Following i.c.v. injection of 25 micrograms or 50 micrograms of choline, heart rate did not change, while 100 micrograms or 150 micrograms i.c.v. choline produced a slight and short lasting bradycardia. Choline (150 micrograms) failed to alter the circulating residual volume of blood in haemorrhaged rats. 2. The pressor response to i.c.v. choline (50 micrograms) in haemorrhaged rats was abolished by pretreatment with mecamylamine (50 micrograms, i.c.v.) but not atropine (10 micrograms, i.c.v.). The pressor response to choline was blocked by pretreatment with hemicholinium-3 (20 micrograms, i.c.v.). 3. The pressor response to i.c.v. choline (150 micrograms) was associated with a several fold increase in plasma levels of vasopressin and adrenaline but not of noradrenaline and plasma renin. 4. The pressor response to i.c.v. choline (150 micrograms) was not altered by bilateral adrenalectomy, but was attenuated by systemic administration of either phentolamine (10 mg kg-1) or the vasopressin antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2,Arg8]-vasopressin (10 micrograms kg-1). 5. It is concluded that the precursor of acetylcholine, choline, can increase and restore blood pressure in acutely haemorrhaged rats by increasing central cholinergic neurotransmission. Nicotinic receptor activation and an increase in plasma vasopressin and adrenaline level appear to be involved in this effect of choline.