Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens.

RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. METHODS: A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 µg/day, 40 µg/day, and 125 µg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. RESULTS: In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. CONCLUSIONS: The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

Warthin's tumor distribution within the parotid gland. A feasible etiologic source from lymph nodal tissue.

AIM: Warthin's tumor (WT) is the second commonest parotid gland neoplasm after pleomorphic adenoma (PA). It mainly arises from the lower pole of the superficial parotid lobe (i.e., tail of gland), a site with the greatest distribution of intra-parotid lymph nodes, and its definitive etiopathogenesis is still unclear. The aim of this study was to support the strict topic and etiologic link hypothesised between this tumor and the intraparotid lymph nodes, as being massively present in the tail, by assessing the WT distribution within the parotid gland. METHODS: Seventy-one WTs excised from 64 patients were compared retrospectively with 134 PAs from 133 patients, as controls. In all sample, staging of parotid gland tumors was defined by sonography and magnetic resonance imaging. Furthermore, tumor localization, size, bilaterality and multifocality were assessed according to radiological, intraoperative and histopathological findings. RESULTS: WTs were mainly detected in the tail (73%), less in the superficial lobe (23%) and the deep one (4%). WT presented with bilateral and synchronous lesions in 10% of cases vs. 0.75% of controls. CONCLUSION: Since the tail has been well known to present the greatest distribution of intra-parotid lymph nodes, our clinical findings on WT parotid localization could suggest the possible origin of this tumor from epithelial salivary gland ductal inclusions, as being likely entrapped during embryogenesis within the intra-parotid lymph nodes, and could support the hypothesis of a heterotopy in the pathogenesis of WT. However, this suggestive hypothesis based only on clinical and "topographic" data should be confirmed by histopathological studies about the presence of the salivary ductal elements trapped within the intra-parotid lymph nodes.

Squamous cell carcinoma arising from long-term (50-year) Lupus vulgaris: is there a need for a close medical follow-up in such chronic diseases?

Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are represented by miliary tuberculosis of the skin, tuberculous chancre, scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and lupus vulgaris (LV). Among this group, LV is the most common skin condition, diagnosed in 10% of tuberculotic patients. The authors report herein a case of squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and underline the need of an extensive follow-up of tuberculotic lesions.

Surgical treatment with Ligasure Precise of schwannoma of brachial plexus: case report.

English version We present a case of bulky schwannoma arising from the brachial plexus treated by a new surgical device. A 38-year-old man presented with a slow-growing left-sided supraclavicular mass and complained paresthesia of the third and forth fingers of the hand and forearm weakness. Physical examination revealed Tinel's sign. A CT-scan revealed a solid mass situated in the left profound supraclavicular fossa. The tumour was resected with the utilization of bipolar vessel sealing system (Ligasure Precise). This device is very useful in sutureless removal of masses localized in deep supraclavicular fossa. During the operation, care was taken to preserve the nerve function.

3-Methoxy-4-hydroxyphenylglycol and primary depression: clinical and pharmacological considerations.

Pretherapeutic urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was studied in 25 primary depressed patients. The results indicate that: (i) There exists a wide variability among primary depressives with respect to MHPG excretion. (ii) Age of onset together with polarity of the disease may account for the nonhomogeneous division of the patients according to MHPG levels. (iii). The other variables considered, with the possible exception of motor activity, do not explain the dichotomy between high or normal and low MHPG levels, even though it is possible that they influence MHPG excretion to some extent, with the consequent possibility of errors in subclassification of the patients at the boundaries between the two groups. (iv) The correlation between motor retardation and low MHPG excretion is positive, but probably due to a frequent association between this motricity state and primary depression of bipolar early onset type. (v) Treatments with chlorimipramine and, to a lesser degree of specificity, with amitriptyline are particularly indicated in patients with normal or high MHPG. Some practical and theoretical implications deriving from these data are briefly discussed.

A biotin-avidin sandwich enzyme-linked immunosorbent assay of growth hormone in bovine plasma.

Purified pituitary bovine growth hormone (bGH) has been used to develop a homologous sandwich enzyme-linked immunosorbent assay in which affinity-purified antibodies are immobilized on microtiter plates. Bovine GH bound to specific antibody is then revealed with a second anti-bGH antibody labeled with biotin and peroxidase-conjugated avidin. The method requires only 48 h, including the coating step, and has a sensitivity as low as 0.25 ng/ml of bGH. Statistical analyses (test of parallelism, cross-reactivity among bGH and GH of various species and bovine prolactin, recovery test, within- and between-assay variation, comparison with radioimmunoassay) confirm the high specificity and reproducibility of the method.

Gas chromatographic determination of urinary 3-methoxy-4-hydroxyphenylethyleneglycol sulphate after its ion-pair extraction.

In order to develop a gas chromatographic method with flame ionization detection for the analysis of urinary 3-methoxy-4-hydroxyphenylethyleneglycol sulphate, a new procedure for its isolation has been introduced. The conjugated metabolite has been extracted by an ion-pair technique using tetrabutyl ammonium as counter ion and dichloromethane as organic solvent. Hydrolysis and derivatization of 3-methoxy-4-hydroxyphenylethyleneglycol sulphate have been finally performed by treatment with heptafluorobutyric anhydride. Each step of the procedure, applied to the analysis of urine samples both from normal subjects and from patients with neuroblastoma, has been discussed.

Determination of 3,4-dihydroxyphenylethyleneglycol in urine by gas chromatography with a flame ionization detector: a new rapid method.

3,4-Dihydroxyphenylethyleneglycol, a major metabolite of noradrenaline in rat brain, is estimated alone or with 4-hydroxy-3-methoxyphenylethyleneglycol in rat and human urine by gas chromatography with a flame ionization detector. The samples are hydrolyzed and extracted at pH 2 with ethyl acetate. Then, to analyze only 3,4-dihydroxyphenylethyleneglycol the reaction with n-butaneboronic acid is carried out directly; if 4-hydroxy-3-methoxyphenylethyleneglycol also has to be estimated, preliminary acetylation in alkaline aqueous solution is performed. The advantages of the specificity due to the reagents used is discussed.

Substitution of fish species detected by thin-layer isoelectric focusing and a computer-assisted method for the evaluation of gels.

Fourteen fish species susceptible to substitution were analysed by the thin-layer isoelectric focusing technique on polyacrylamide gels of pH 3.5-9.5. Four fish per species were run on the same gel to verify the possibility to differentiate them according to their protein banding patterns. The occurrence of intraspecific differences due either to electrophoretic variations or to protein polymorphism was also observed. In fact, some of them showed few dissimilarities among their protein profiles. However, the differentiation was possible for all species, even for those belonging to the same order, family and genus. Computer-based tools combined with statistical analysis were implemented and usefully applied to avoid a subjective evaluation of the isoelectric focusing gels, and to verify the reliability of the preliminary visual comparison of protein patterns.

Gas chromatographic determination of galactose in milk. Example of a switching valve used for the protection of the capillary column.

Galactose, a marker of heat treatment, has been analysed in milk as pentafluorobenzyloxime acetate by gas chromatography with flame ionization detection using a simple switching valve system. The procedure did not entail any prederivatization clean-up for lactose elimination from the sample. In a short pre-column, reagent and lactose derivative excess were separated and the galactose and internal standard derivatives were transferred to the analytical column by a four-port valve. Thus, the analytical column was protected from overloading, so avoiding rapid deterioration.

Age-related differences of blood pressure profile in essential hypertension.

The purpose was to assess age-related circadian changes of blood pressure profile (BPP) employing a truncated Fourier series with four harmonics (tFs) in patients with essential hypertension. The study was performed on 32 patients with essential hypertension divided in two groups: (A) 15 patients younger than 55 years and (B) 17 patients older than 60 years. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored every 20 minutes for 24 h with a noninvasive portable device (SpaceLabs 90202). To evaluate the existence of SBP and DBP circadian rhythms a one-sample runs-test was performed and the mesor, amplitude, and acrophase from the overall curve of each patient were obtained by tFs. In both groups, SBP and DBP profiles showed a first peak in the late morning and a second peak in the early evening around the same hours. The two peaks in the SBP profile were higher and the two peaks in the DBP profile were lower in older patients than in younger ones (p < .01, p < .05, p < .3, p < .05). The truncated Fourier series with four harmonics evidences different age-related BP profiles characterized by two peaks with higher SBP and lower DBP in elderly patients. These changes of BPP are in accordance with the reported higher risk of cardiovascular events observed around the same hours.

A simplified procedure for purification of bovine growth hormone on Sephacryl S-200 superfine.

The isolation and purification of bovine growth hormone from pituitary glands by a shorter and efficient sequence of stages which utilizes the Reichert approach (Reichert, 1975) is described. The major innovations are: 1) precipitation in 2 M ammonium sulfate at pH 7.9 instead of pH 7.0 to obtain the extract designated as C-2 by Reichert and 2) early gel-chromatography on Sephacryl S-200 of the C-2 extract. The bGH obtained has higher specific activity than the standard reference hormone NIH-GH-B16. Electrophoretic and size homogeneity is investigated by isoelectric focusing and sodium dodecyl sulfate electrophoresis.

A new procedure for the specific high-performance liquid chromatographic determination of hydroxyproline.

A procedure suitable for a selective high-performance liquid chromatographic (HPLC) analysis of the imino acid hydroxyproline in the presence of a large excess of amino acids is proposed. To deaminate the amino acids, the well-known reaction with nitrous acid is exploited. The N-nitroso derivatives of imino acids obtained are extracted in ethyl acetate, denitrosated by hydrobromic acid, and treated with dabsyl-chloride. The final HPLC separations are carried out on a reversed-phase column in a rapid isocratic run. The use of the cis isomer of hydroxyproline as an internal standard allows good reproducibility. As an application of the described method, the hydroxyproline content in samples containing collagen and an excess of bovine serum albumine (up to 20:1) is determined.

[Controlled trabeculectomy and incidence of postoperative choroidal detachment]. / Kontrollierte Trabekulektomie und Häufigkeit der postoperativen Aderhautamotio.

In this study the authors report their experience with titrated trabeculectomy. It is performed as follows: tight scleral flap trabeculectomy, five or more 10/0 nylon sutures, argon laser lysis of one or more sutures (depending on the eye's postoperative condition) by means of the Hoskins lens. The aim of this technique, performed by the authors for 3 years, is to decrease atalamia and choroidal detachment. Results obtained in 70 eyes of 62 patients with chronic open-angle glaucoma are compared by means of statistical analysis with those in 70 eyes of 66 patients operated on by means of the traditional technique. The incidence of choroidal detachment is significantly reduced (P < 0.001). There is no important difference in ocular pressure and visual acuity. In conclusion, this technique is very useful in controlling and titrating the filtration rate, avoiding an excessive lowering of IOP after trabeculectomy and decreasing the complications.

[Efficacy and safety of ambulatory electric cardioversion of atrial fibrillation with monophasic and biphasic shock]. / Efficacia e sicurezza della cardioversione elettrica della fibrillazione atriale in regime di day-hospital con shock mono e bifasico.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of ambulatory external cardioversion (EC) by means of monophasic and biphasic shock in patients with persistent atrial fibrillation (AF). METHODS: One hundred and twenty-seven consecutive patients with AF were submitted to EC, preceded by short general anesthesia with propofol, after pretreatment with oral anticoagulants for at least 3 weeks and, if not contraindicated, with amiodarone. In 87 of these patients we used monophasic shock and in 40 patients we used biphasic shock. Our protocol provided for up to 3 shocks delivered at an energy level ranging between 200 and 360 J for monophasic and from 70 to 175 J for biphasic shock. The patients were discharged after 4 hours of ECG monitoring and following a determination of serum CK-MB at the fourth hour. RESULTS: The mean age of the patients submitted to EC with monophasic and biphasic shock (65 +/- 9 vs 67 +/- 7 years) and the duration of AF (34 +/- 22 vs 32 +/- 25 days) were similar. The efficacy of EC with monophasic shock was 85% and the mean energy delivered was 266 +/- 81.5 J. The efficacy of the EC with biphasic shock was 98% and the mean energy delivered was 127 +/- 40 J. The difference between the percentage of efficacy and the number of joules delivered was statistically significant (p < 0.05). The mean value of the CK-MB after 4 hours following delivery of the shock was not significantly different: 2.5 ng/ml for monophasic vs 1.7 ng/ml for biphasic shock (p = NS). CONCLUSIONS: In our patients, ambulatory EC of persistent AF is safe and feasible; biphasic shock is more efficacious and requires less energy with respect to monophasic shock.

Effect of risedronate in osteoporotic HIV males, according to gonadal status: a pilot study.

The aim of the study was to evaluate the effect of risedronate on bone mineral density (BMD) and bone turnover markers in HIV-infected osteoporotic males, according to their gonadal status. HIV patients were followed up for 24 months and divided into two groups: patients with osteoporosis or osteopenia with fractures (group A, n = 20) and those without (group B, n = 21). Group A and B were further divided according to the presence of reduced androgenizations. Both groups were treated with cholecalciferol 800 I.U. and calcium (Ca) 1,000 mg orally every day for the first 12 months. Risedronate 75 mg for two consecutive days a month orally was then added in group A, for another 12 months. Group B continued treatment with Ca and vitamin D. Every 6 months each patient underwent biochemical evaluation, and BMD measurement. A significant increase in lumbar BMD was observed in HIV males with adequate androgenization after 12 months of risedronate treatment in group A together with a reduction of bone turnover markers. BMD remained stable with a concomitant significant slight reduction of bone turnover markers in group B. Risedronate increased BMD and reduced bone turnover markers to a greater extent in patients with adequate androgenization compared to osteoporotic HIV males with symptomatic hypoandrogenization.