Vitamin D Insufficiency in Greenlanders on a Westernized Fare: Ethnic Differences in Calcitropic Hormones Between Greenlanders and Danes

We studied the influence of age, gender, latitude, season, diet and ethnicity on plasma 25-hydroxyvitamin D 25 OHD, PTH, 1,25-dihydroxyvitamin D, vitamin D-binding protein, bone-specific alkaline phosphatase, and osteocalcin levels in 46 Greenlanders living in Nuuk (64°N) on a traditional fare (group A), 45 Greenlanders living in Nuuk on a westernized fare (group B), 54 Greenlanders (group C), and 43 Danes (Group D) living in Denmark (55°N) on a westernized fare. Blood specimens were drawn both summer and winter. Vitamin D insufficiency (plasma 25 OHD <40 nmol/l) was common in all four study groups during summer (23–74%) and winter (42–81%). Compared to groups A and D, vitamin D insufficiency was significantly more frequent in groups B and C. In all groups, summer levels of 25 OHD were above winter levels. Multiple regression analysis revealed a significant effect of ethnicity. Compared to Danes, Greenlanders had higher 1,25-dihydroxyvitamin D levels, but lower 25 OHD and PTH levels despite relatively low plasma calcium concentrations. In addition to ethnicity, 25(OH)D levels were influenced by age, season (summer > winter), and diet (a traditional Inuit diet>westernized diet). Ethnical differences exist between Greenlanders and Danes. Our results suggest that Greenlanders may have an inherent lower set-point for calcium-regulated PTH release or an enhanced renal 1,25(OH)₂D production. In addition to ethnicity, age, season, and diet were important determinants of vitamin D status. Changes from a traditional to a westernized fare are associated with a reduced vitamin D status in Greenlanders. Vitamin D supplementation should be considered.     

Steroid injection to vocal nodules using fiberoptic laryngeal surgery under topical anesthesia

Since 1990, we have performed steroid injection into the vocal fold by fiberoptic laryngeal surgery (FLS) under local anesthesia. In this study, the usefulness of this method was evaluated in 28 patients with vocal nodules. Under monitoring using a fiberoptic laryngoscope, a curved injection needle was inserted via the oral cavity and steroid was injected. Endoscopic findings showed that the vocal nodule had disappeared in 17 patients of the 27 patients and decreased in 10 after injection. The maximum phonation time was 10.9 s before operation and 13.9 s after operation, showing a significant increase (P<0.05), and the mean flow rate also showed a significant improvement (P<0.05). The patients self-rating concerning hoarseness demonstrated great improvement after injection. This technique can be performed under local anesthesia in combination with voice therapy on an outpatient basis, and it is considered to be useful for treating vocal nodules.     

Management of unresponsive asthma

Difficult asthma is defined as asthma that is not controlled despite treatment with <>800 ug budesonide or equivalent per day. Poor control is defined as the need for bronchodilators more than three times a week, school absence of more than five days a term, or one episode or more of wheezing each month. Common causes of poor response to treatment include; wrong diagnosis, inappropriate medications or improper inhalation technique, poor adherence to medications and co-morbidity. Steroid resistant asthma is uncommon and estimated to be 1 in 1000–10000 asthmatic patients. If there is no functional improvement to prednisolone 2 mg/kg/day for 2 weeks with adherence checked by measuring serum prednisoloneand cortisol levels, a fibreoptic bronchoscopic examination with bronchoalveolar lavage and large airway biopsy should be considered. Eosinophilic inflammation identified on the biopsy in a child who is unresponsive to prednisolone may benefit from alternative anti-inflammatory treatments such as cyclosporin. Neutrophilic infiltration in biopsy may benefitwith macrolide antibiotics, 5-lipogenase inhibitors or theophyllines.     

Intravenous immunoglobulin therapy for acute cerebellar ataxia

A case of acute cerebellar ataxia without any prodromal illness showed cerebellar hypoperfusion on 123 I-iodoamphetamine single photon emission computed tomography. The symptoms did not resolve spontaneously or with methylprednisolone pulse therapy but disappeared rapidly with intravenous immunoglobulin therapy.

Conclusion: Intravenous immunoglobulin therapy is worth considering in acute cerebellar ataxia that does not respond to high-dose steroid therapy.     

Doping control for nandrolone using hair analysis

A sensitive, specific and reproducible method for the quantitative determination of nandrolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml NaOH IN, 15 min at 95°C, in presence of 10 ng nandrolone-d₃ used as an internal standard. The homogenate was neutralized and extracted using consecutively a solid phase (Isolute C18) and a liquid–liquid (pentane) extraction. The residue was derivatized by adding 50 μl MSTFA/NH4I/2-mercaptoethanol (1000:2:5; v/v/v), then incubated for 20 min at 60°C. A 4-μl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl–95% methylsiloxane, 30 m×0.25 mm i.d.×0.25 mm film thickness) of a Hewlett Packard (Palo Alto, CA) gas chromatograph (6890 Series) via a Hewlett Packard (7673) autosampler. The assay was capable of detecting 0.5 pg of nandrolone per mg of hair when approximately 100 mg of hair were processed. Linearity was observed for nandrolone concentrations ranging from 1 to 50 pg/mg with a correlation coefficient of 0.997. Intra-day and between-day precisions at 10 pg/mg were 11.2 and 15.1%, respectively, with an extraction recovery of 81.7%. The analysis of three strands of hair, obtained from three bodybuilders, revealed the presence of nandrolone at the concentration of 1, 3.5 and 7.5 pg/mg.     

Prenatal diagnosis and treatment of steroid 21-hydroxylase deficiency (congenital adrenal hyperplasia)

Steroid 21-hydroxylase deficiency congenital adrenal hyperplasia is the most common cause of genital ambiguity in females at birth. Inhibited formation of cortisol causes increase in the release of ACTH in turn leading to overproduction of adrenal androgens. This predisposes the affected female fetus to prenatal development of genital ambiguity. A large number of patients also have aldosterone insufficiency which manifests after birth in form of inability to conserve sodium and to excrete potassium which can lead to adrenal shock and neonatal death, if left untreated. Prenatal diagnosis is possible using several methods like steroid assay of amniotic fluid and,HLA typing. Recently with advancement more accurate direct molecular genetic techniques have been utilized on chorionic villus samples in first trimester of pregnancy. Prenatal treatment is also possible and pregnancies can be managed by administering dexamethasone to the mother as soon as pregnancy is diagnosed. This suppresses fetal androgen production in genetic females preventing virilization and leading to normal development. Prenatal diagnosis and treatment are highly desirable in families with a positive family history towards birth of a child without features of the disease.     

Steroid-responsive bilateral sensorineural hearing loss and immune complexes

Summary We have recognized in recent years that some cases with idiopathic bilateral sensorineural hearing loss which showed acute progression in either ear responded to steroid and that the improved hearing level could be maintained by longterm administeration of steroid only.Forty cases of bilateral sensorineural hearing loss were selected for study. In most of these cases hearing deterioration of either ear was confirmed by audiometry.Eight of fifteen cases with marked improvement have been proved to respond to steroid treatment. These eight cases include three cases with syphilitic deafness and one case with aortitis syndrome. In four other cases the causes are still unknown, but could be due to autoimmune mechanisms. In four of 25 cases the immune complexes (IC) value was higher than normal and three among them responded to steroid.Since a high IC value has been reported in lupus nephritis, immunologic examinations are necessary for patients over 30 years of age with bilateral sensorineural hearing loss.     

酒精和激素性股骨头缺血性坏死发病机制的实验研究

目的研究酒精和激素性股骨头缺血坏死的发病机制。方法选用健康成熟的中国白兔６０只,体重２．５±０．５ｋｇ,雌雄不限,随机分成两组。Ａ组３０只为酒精组,Ｂ组３０只为激素组。分别于实验前和实验后２、４、６、８周测血脂、前列腺素Ｅ２和血栓烷素Ｂ２。并于第４、８、１０周分批处死,取肝脏和股骨头作常规病理组织学和超微结构观察。结果两组血脂水平明显升高,差异无显著性意义;从实验第４周开始两组前列腺素Ｅ２较处理前明显增高（Ｐ＜０．０１）;而实验第４周和第８周前列腺素Ｅ２的含量Ａ组较Ｂ组明显增高（Ｐ＜０．０１）。两组动物都出现股骨头骨细胞坏死,同时有大量骨细胞发生脂肪变性及坏死。电镜下两实验组可见股骨头部骨细胞内出现异常增多的脂滴,核变性深染,细胞器消失。但Ａ组动物骨细胞坏死程度比Ｂ组动物严重,表现为损伤作用强烈,经过急剧,呈急性坏死表现。而Ｂ组动物骨细胞坏死呈慢性进行性坏死表现。结论激素所致的股骨头缺血坏死是多种因素引起股骨头血液循环障碍,导致骨坏死;而酗酒使血中游离脂肪酸升高,前列腺素增多,易发生血管炎而栓塞,以致骨缺血坏死     

Crucial Role of 3-Bromoethyl in Removing the Estrogenic Activity of 17β-HSD1 Inhibitor 16β-(m-Carbamoylbenzyl)estradiol

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) represents a promising therapeutic target for breast cancer treatment. To reduce the undesirable estrogenic activity of potent 17β-HSD1 inhibitor 16β-(m-carbamoylbenzyl)estradiol (1) (IC(50) = 27 nM), a series of analogues with a small functionalized side chain at position 3 were synthesized and tested. The 3-(2-bromoethyl)-16β-(m-carbamoylbenzyl)-estra-1,3,5(10)-trien-17β-ol (5) was found to be a potent inhibitor (IC(50) = 68 nM) for the transformation of estrone (E1) into estradiol (E2) and, most importantly, did not stimulate the proliferation of estrogen-sensitive MCF-7 cells, suggesting no estrogenic activity. From these results, the crucial role of a bromoalkyl side chain at carbon 3 was identified for the first time. Thus, this new inhibitor represents a good candidate with an interesting profile suitable for further studies including pharmacokinetic and in vivo studies.     

The steroid effect on the blood-ocular barrier change induced by triolein emulsion as seen on contrast-enhanced MR images.

OBJECTIVE: The purpose of this study is to evaluate the effect of dexamethasone on the damaged blood-ocular barrier caused by triolein emulsion, using contrast-enhanced MR imaging. MATERIALS AND METHODS: An emulsion of 0.1-mL triolein in 20 mL of saline was infused into the carotid arteries of 32 cats, 12 cats were placed in the treatment group and 18 cats were placed in the Control group. Thirty minutes after the infusion of triolein emulsion, a set of orbital pre- and post-contrast T1-weighted MR images (T1WIs) were obtained. Infusion of 10 mg/kg dexamethasone into the ipsilateral carotid artery of each of the cats in the treatment group cats and 20 mL saline in each of the cats in the control group was given. A second set of pre- and post-contrast orbital T1WIs were obtained three hours following triolein emulsion infusion. Qualitative analysis was performed for the the anterior chamber (AC), the posterior chamber (PC), and in the vitreous humor of the ipsilateral and contralateral eyes. The signal intensity ratios of the ipsilateral eye over the contralateral eye were quantitatively evaluated in the three ocular chambers on the first and second set of T1WIs, and were then statistically compared. RESULTS: Qualitatively, the AC, the PC or the vitreous did not show immediate contrast enhancement on the first and the second set of post-contrast T1WIs. However, the AC and the PC showed delayed contrast enhancement for both groups of cats on the second pre-contrast T1WIs. No enhancement or minimally delayed enhancement was seen for the vitreous humor. Quantitatively, the signal intensity ratios in the PC of the treatment group of cats were statistically lower than the ratios of the control group of cats for the second set of T1WIs (p = 0.037). The AC and vitreous showed no statistically significant difference between the feline treatment group and control group (p > 0.05). CONCLUSION: Contrast-enhanced MR images revealed increased vascular permeability in the PC of the eye after infusion of triolein emulsion. Dexamethasone seems to decrease the breakdown of the blood-aqueous barrier in the PC.