Response of different PTH assays to therapy with sevelamer or CaCO<Subscript>3</Subscript> and active vitamin D sterols

Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation. However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined. In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to 8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO₃) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl during CaCO₃ therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO₃ and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and 932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients treated with sevelamer received higher doses of vitamin D than those treated with CaCO₃. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels.     

Spontaneous intracranial hypotension manifesting as an amnestic syndrome

Journal of Neurology -     

Pseudoaneurysm following vertebral biopsy and treatment with percutaneous thrombin injection

We present a case of a pseudoaneurysm within the lumbar musculature. This occurred following a computed tomography (CT)-guided vertebral biopsy in a 79-year-old male patient and was successfully treated with percutaneous ultrasound-guided thrombin injection. The patient initially presented with severe back pain. The plain radiographs and Magnetic resonance imaging (MRI) showed destruction of the L1 and L2 end plates, with marked narrowing of the disc space, suggestive of infective discitis. CT-guided biopsy was performed by the right paravertebral approach. Methicillin-resistant Staphylococcus aureus (MRSA) was grown, following culture of the specimen. Twenty days later, the patient developed a palpable swelling in the right lumbar region, with worsening of the back pain. MRI and ultrasound imaging showed a 3 cm pseudoaneurysm within the right lumbar musculature. The pseudoaneurysm was successfully treated following percutaneous ultrasound-guided injection of thrombin.     

Identification of the putative bryostatin polyketide synthase gene cluster from "Candidatus Endobugula sertula", the uncultivated microbial symbiont of the marine bryozoan Bugula neritina

The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium "Candidatus Endobugula sertula" ("E. sertula"). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a beta-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related "E. sertula" strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are added by the HMG-CS gene cassette. The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical.     

Iron deficiency in children with early chronic kidney disease

Iron deficiency (ID) contributes to the development of anemia in patients with chronic kidney disease (CKD). The frequency of ID in children with early CKD has not previously been reported. This was a retrospective chart review of children with CKD stages 2 and 3 followed at the CKD clinic of Children’s Hospital of Michigan. ID was defined as low ferritin and transferrin saturation <20%. Patients on iron supplements were considered as iron-deficient cases. There were 50 patients included in the study (72% male) with a mean age of 10.31 (±5.21). The mean glomerular filtration rate (GFR) was 55.4 ml/min/1.73 m² (±14.61). ID was present in 42% of patients, out of whom almost half (42.9%) presented with anemia. Females had a higher frequency of ID (64.3%). The frequency of ID with anemia increased from 4.3% to 29.6%, (p = 0.03) in stage 2 to stage 3 CKD, respectively. The frequency of ID without anemia also increased with progression of CKD from stage 2 to stage 3, however, the difference was not statistically significant. ID is frequent in patients with early CKD. Monitoring of iron tests and treatment of ID is important in this population of patients.     

An evaluation of flexible intramedullary nail fixation in femoral shaft fractures in paediatric age group

Sixty-two femoral shaft fractures in 60 patients treated by elastic intramedullary nailing with mean age of the patients being 9.2 years (range 5 years to 12 years) and average follow-up of 15 months (range 7 months to 60 months) are evaluated. Twenty-eight fractures were fixed with titanium elastic nail while 34 fractures were fixed with Enders nail. There were 40 midshaft fractures, 18 proximal femoral and 4 were fractures of distal third. Fracture patterns were transverse in 35, short oblique in 14 cases and 13 were spiral fractures. Mean age of union in this series was 17 weeks (range 12 weeks to 28 weeks). Ten cases had complications, 5 had nail tip irritation, 3 varus or valgus malalignment and 2 had delayed union. In this series, we did not have any non-union, refracture, limb length discrepancy or any major infection. The result demonstrates 100% union rate irrespective of the age, weight and height of the patient. Regardless of the site of fracture and their pattern, it united every time with elastic nail fixation. We did not find and mismatch in the results of fractures stabilised with titanium elastic nail with that of elastic stainless steel nail.     

Primary Sellar Neuroblastoma Presenting with Syndrome of Inappropriate Secretion of Anti-diuretic Hormone

A 29-year-old Ethiopian man presented with marked bilateral visual loss, headache, hypopituitarism and significant hyponatraemia (115 mmol/L). A brain MRI scan demonstrated a large, lobulated, sellar and suprasellar mass, elevating the floor of the 3rd ventricle and compressing the optic chiasm. The patient underwent a transphenoidal resection of the mass followed by a craniotomy 10 days later. Histological examination demonstrated a Hyams’ grade III neuroblastoma with ectopic expression of vasopressin. He underwent fractionated radiotherapy at a dose of 60 Gy in 30 fractions. Fourteen months after the onset, he is well with no neuroimaging evidence of tumour recurrence. His serum and urine sodium are completely normalised.     

Nasal-nanotechnology: revolution for efficient therapeutics delivery

Context: In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose.

Objective: The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration.

Methods: Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration.

Results and conclusion: The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.     

In Vitro and In Vivo Toxicity Evaluation of Natural Products with Potential Applications as Biopesticides

The use of natural products in agriculture as pesticides has been strongly advocated. However, it is necessary to assess their toxicity to ensure their safe use. In the present study, mammalian cell lines and fish models of the zebrafish (Danio rerio) and medaka (Oryzias latipes) have been used to investigate the toxic effects of ten natural products which have potential applications as biopesticides. The fungal metabolites cavoxin, epi-epoformin, papyracillic acid, seiridin and sphaeropsidone, together with the plant compounds inuloxins A and C and ungeremine, showed no toxic effects in mammalian cells and zebrafish embryos. Conversely, cyclopaldic and α-costic acids, produced by Seiridium cupressi and Dittrichia viscosa, respectively, caused significant mortality in zebrafish and medaka embryos as a result of yolk coagulation. However, both compounds showed little effect in zebrafish or mammalian cell lines in culture, thus highlighting the importance of the fish embryotoxicity test in the assessment of environmental impact. Given the embryotoxicity of α-costic acid and cyclopaldic acid, their use as biopesticides is not recommended. Further ecotoxicological studies are needed to evaluate the potential applications of the other compounds.