甲真菌病治疗指南

该指南是英国皮肤科医师协会针对皮肤科医生制定的 ,反映了当前文献报道中的最新研究资料。在解释这些资料时应慎重 ,因为未来的研究可能会改变现有的结论或推荐方案。在应用该指南时 ,需因人而异 ,因地制宜。遵守指南并不能确保万无一失 ,因此对实施指南时的偏离不应都归咎于疏忽 (该指南并不能保证面面俱到 ,在实际应用中可加以变通 )。简介 :甲真菌病是最常见的皮肤病之一。英国对 10 0 0 0人进行的一项大规模问卷调查显示发病率为 2 71%。芬兰和美国最近的真菌学对照调查表明 ,发病率为 7%～ 10 %。甲真菌病发病率的升高和有效抗真菌新…     

Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial

OBJECTIVE: To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI. RESEARCH DESIGN AND METHODS: This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment. RESULTS: At t = 0, HbA1c was 9.2 +/- 0.9%, insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6 +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups. CONCLUSIONS: Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.     

Modulation of megakaryocytopoiesis by human basic fibroblast growth factor

Basic fibroblast growth factor (bFGF) may act to modulate hematopoiesis in addition to its effects on mesenchymal cells. We studied the effects of bFGF on human and murine primary marrow megakaryocytes. bFGF modestly enhanced the size of the human megakaryocyte colony-forming unit (CFU-MK) and cell numbers per colony, in combination with interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Adhesion of human megakaryocytes to bone marrow (BM) stromal fibroblasts was enhanced when either stromal fibroblasts or megakaryocytes were treated with bFGF. This resulted in significantly increased proliferation of megakaryocytes. In addition, bFGF augmented secretion of the cytokines tumor necrosis factor alpha and IL-6 by human primary BM megakaryocytes. Immature murine megakaryocytes showed a significant growth response to bFGF as measured by the single cell growth assay. This effect was abrogated by specific antibodies for bFGF and combination of anti-IL-6 and anti-IL-1 beta antibodies. bFGF has no effect on murine CFU-MK formation, but significantly potentiated CFU-MK formation in the presence of IL-3 or GM-CSF. These results indicate that the effect of bFGF on various megakaryocyte populations is different and that bFGF may affect megakaryocytopoiesis via modulation of megakaryocyte-stromal interactions and via augmentation of cytokine secretion from megakaryocytes.     

Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma [see comments]

Interleukin-10 (IL-10) is an acid-sensitive protein of 35 kD that has pleiotropic effects including inhibition of cytotoxic T-cell response, induction of major histocompatibility complex type II in B lymphocytes, induction of B-cell growth and differentiation, and autocrine growth factor activity in monocytes. We and others have shown that IL-10 is produced spontaneously by blood mononuclear cells from human immunodeficiency virus-seropositive patients. In an attempt to ascertain the potential role of IL-10 in acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, we evaluated the expression of human IL-10 in both tumor-derived B-cell lines and primary tumor cells. Expression of human IL-10 (hIL-10) mRNA and protein was detected in four of five cell lines examined. An IL-10 antisense oligonucleotide inhibited IL-10 mRNA expression and IL-10 protein production. The proliferation of all B-cell lines was inhibited by an antisense oligonucleotide in a dose-dependent manner that was abrogated by the addition of recombinant hIL-10 protein. No effect of antisense oligonucleotide was observed in the B-cell line not producing hIL-10. Evaluation of primary tumor cells from patients with AIDS-lymphoma cells showed similar production and response to IL-10. These data suggest an autocrine growth mechanism for IL-10 in AIDS-related lymphoma cells and that IL-10 may be important in its pathogenesis.     

Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women

Women with ovarian hyperandrogenism frequently have insulin resistance, whose underlying mechanism remains to be determined. In the present study we have investigated the relationship between insulin sensitivity and the acute effect of endogenous insulin secretion on circulating androgen levels. Insulin sensitivity, glucose-mediated insulin release, and glucose/insulin-stimulated androgen responses were determined during a frequently sampled iv glucose tolerance test in a group of 19 women with clinical evidence of polycystic ovary syndrome (PCOS) and 9 age- and weight-matched controls. Insulin (I), glucose, androstenedione, testosterone (T), free T, and dehydroepiandrosterone (DHEA) levels were measured before and during the 3 h following iv administration of glucose (300 mg/kg). Intravenous tolbutamide (300-500 mg) was injected 20 min after the glucose injection. Insulin sensitivity (SI) was calculated by application of the minimal model of glucose kinetics. Fasting androstenedione, T, free T, and I concentrations were significantly higher in the women with PCOS than in controls (P less than 0.02). In PCOS subjects, fasting I was correlated with both T (r = 0.51; P less than 0.05) and DHEA (r = 0.706; P less than 0.01). SI was significantly lower in PCOS subjects [SI, 68.35 +/- 8.34 min-1/(nmol/mL] than in control subjects (SI, 133.36 +/- 21.7 min-1/(nmol/mL)]. A significant decline in DHEA levels was observed in control subjects 3 h after glucose administration (from 28.4 +/- 3.0; final, 16.2 +/- 2.4; P less than 0.02). PCOS women with normal insulin sensitivity [SI, greater than 75.0 min-1/(nmol/mL)] showed a similar fall in DHEA (from 20.3 +/- 2.5 to 12.8 +/- 1.8 nmol/L; P less than 0.02). No significant change occurred in insulin-resistant PCOS subjects [SI, less than 75.0 min-1/(nmol/mL)]. Other androgen levels showed a modest nonsignificant decline during the study in PCOS and control groups. These findings confirm the weight-independent insulin resistance of some hyperandrogenic women. The failure of glucose-stimulated endogenous insulin secretion to significantly depress DHEA levels in insulin-resistant women with PCOS may account in part for their androgen excess.     

Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance.

It has been hypothesized that insulin resistance and hyperinsulinemia contribute to the development of arterial hypertension. To further investigate this relationship, we compared arterial blood pressure in controls and women with polycystic ovary syndrome (PCO), an insulin-resistant state. Fourteen PCO women and 18 normal control women of similar age, body mass index, and race were studied. Plasma glucose and insulin levels were determined in an oral glucose tolerance test. The insulin sensitivity (SI) index was determined by the minimal model method. Systolic and diastolic blood pressure were measured by 24-h ambulatory monitoring. Left ventricular mass was assessed by echocardiography. The two groups had comparable fasting glucose levels, but the 2-h postload glucose was higher in PCO (8.0 +/- 0.5 vs. 5.6 +/- 0.3 mmol/L; P less than 0.001). Compared to controls, PCO women were significantly more insulin resistant by fasting insulin, 2-h insulin concentrations, and SI (28.3 +/- 6.7 vs. 68.3 +/- 10.0 min-1/nmol.mL; P less than 0.01). Average ambulatory systolic (121 +/- 2 vs. 118 +/- 2 mm Hg) and diastolic (76 +/- 2 vs. 73 +/- 2 mm Hg) blood pressures were similar for PCO and control women. No difference was found in left ventricular mass. Therefore, despite profound insulin resistance and hyperinsulinemia, women with PCO do not have increased arterial pressure or left ventricular mass.