1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration.

BACKGROUND: The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans. METHODS: Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17,739). RESULTS: In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries. CONCLUSIONS: Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life.     

Digital imaging of the chest

During the past several years, image acquisition in nuclear medicine, computed tomography, ultrasonography, subtraction angiography, and magnetic resonance has been by digitization. Despite these advances, research in the development of digital imaging in conventional radiography has lagged behind. Although studies with a variety of digital techniques have been carried out on several fronts, we still do not possess a method that has captured the imagination of the majority of radiologists and other physicians to a point where it could replace conventional screen-film imaging. This article reviews the current status and general principles of the technology, focusing on the four digital radiographic techniques that have shown the greatest promise - film digitization, an image intensifier - based system, photostimulable phosphor plates, and a scanned projection system. The physical aspects of each of the four systems and the clinical results that have been reported to date, as well as the advantages and disadvantages of each system, are presented.     

Predictors of Ventricular Tachvcardia Inducibility in Programmed Electrical Stimulation and the Effectiveness of Serial Drug Testing: Polish Multicenter Study

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.     

Differences in psychotropic drug prescriptions among ethnic groups in the Netherlands

Background  

Psychotropic drug use in Europe and the USA has increased in the past 20 years. The rise in mental health-care use instigated a debate about possible differences in prevalence rates between different ethnic groups in the Netherlands, although the exact differences were unknown. The aim of this study was to determine whether these minority groups were more or less likely than the native population to receive psychotropic drugs.     

Maternal supplementation with citrulline increases renal nitric oxide in young spontaneously hypertensive rats and has long-term antihypertensive effects

NO deficiency is associated with development of hypertension. Defects in the renal citrulline-arginine pathway or arginine reabsorption potentially reduce renal NO in prehypertensive spontaneously hypertensive rats (SHRs). Hence, we investigated genes related to the citrulline-arginine pathway or arginine reabsorption, amino acid pools, and renal NO in 2-week-old prehypertensive SHRs. In addition, because perinatally supporting NO availability reduces blood pressure in SHRs, we supplemented SHR dams during pregnancy and lactation with citrulline, the rate-limiting amino acid for arginine synthesis. In female offspring, gene expression of argininosuccinate synthase (involved in renal arginine synthesis) and renal cationic amino acid Y-transporter (involved in arginine reabsorption) were both decreased in 2-day and 2-week SHRs compared with normotensive WKY, although no abnormalities in amino acid pools were observed. In addition, 2-week-old female SHRs had much less NO in their kidneys (0.46+/-0.01 versus 0.68+/-0.05 nmol/g of kidney weight, respectively; P<0.001) but not in their heart. Furthermore, perinatal supplementation with citrulline increased renal NO to 0.59+/-0.02 nmol/g of kidney weight (P<0.001) at 2 weeks and persistently ameliorated the development of hypertension in females and until 20 weeks in male SHR offspring. Defects in both the renal citrulline-arginine pathway and in arginine reabsorption precede hypertension in SHRs. We propose that the reduced cationic amino acid transporter disables the developing SHR kidney to use arginine reabsorption to compensate for reduced arginine synthesis, resulting in organ-specific NO deficiency. This early renal deficiency and its adverse sequels can be corrected by perinatal citrulline supplementation persistently in female and transiently in male SHRs.     

Y染色体或将在进化中消失

美国宾夕法尼亚州立大学的2位科学家在性染色体进化变异机制的研究上取得进展。研究发现,Y染色体比X染色体的演化速率快得多,这将导致Y染色体上的基因急剧丢失,如此,Y染色体将会完全消失,人类的传宗接代将受威胁。     

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2)

Background  

We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely.     

Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure

Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.