Evaluation of thyrotoxicosis during pregnancy with color flow Doppler sonography

OBJECTIVE: To determine whether color flow Doppler sonography (CFDS) is useful in differentiating Graves vs non-Graves thyrotoxicosis during pregnancy, when nuclear imaging is contraindicated. METHODS: Ten pregnant women with thyrotoxicosis were divided into Graves, and non-Graves, disease groups and were evaluated by CFDS for thyroid volume, vascularity, and inferior thyroid artery (ITA) flow velocity. Each patient was matched with a euthyroid woman of the same pregnancy duration. RESULTS: Of the 10 patients, 3 were diagnosed with Graves disease, 4 with gestational toxicosis, and 3 with destructive thyroiditis. Those in the Graves disease group had a greater thyroid gland volume (18.9+/-1.5 cm3 vs 12.1+/-2.4 cm3; P<0.05), greater thyroid vascularity, and greater ITA flow velocity than those in the non-Graves disease group (92+/-13 cm/s vs 20.4+/-2.4 cm/s; P<0.05). There was no significant difference in the corresponding values between the patients with gestational toxicosis and those with destructive thyroiditis or between them and their healthy controls. CONCLUSION: Thyroid evaluation by CFDS is useful for the differential diagnosis of thyrotoxicosis in pregnant women.     

Molecular cloning of the guinea pig GRO gene and its rapid expression in the tissues of lipopolysaccharide-injected guinea pigs.

BACKGROUND: CXC chemokines, IL-8 and GRO, play a role in the recruitment of neutrophils in the human. The functional orthologues in the rat and mouse are CINC/KC and MIP-2. The lack of IL-8 made these animals less useful to study the role of IL-8 and GRO. METHODS: Guinea pig (gp) cDNA libraries were screened for GRO and IL-1beta. A gp genomic library was screened with a gpGRO cDNA probe. Expression of gpIL-8, gpGRO, gpTNFalpha, and gpIL-1beta was investigated by Northern analysis and/or by in situ hybridization. RESULTS: Two gpGRO cDNAs, a 3.0-kb gpGRO genomic DNA, and a gpIL-1beta cDNA were cloned. gpGRO and gpIL-8 mRNA were detected in different tissues including lungs 1 h after intraperitoneal injection of lipopolysaccharide (LPS) into guinea pigs. gpGRO, gpIL-8, gpTNFalpha, and gpIL-1beta expression peaked at 3 h in the lungs. Both gpGRO and gpIL-8 mRNA were detected in the cells in alveolar spaces and bronchial epithelial cells. However, gpGRO mRNA, but not gpIL-8, was also expressed in endothelial cells and vascular smooth muscle cells. CONCLUSIONS: gpGRO and gpIL-8 mRNA rapidly accumulated in the lungs of guinea pigs after LPS injection. Expression of gpIL-8 and gpGRO mRNA appeared to be independent from TNFalpha- or IL-1beta-stimulation in this model. A high level expression of gpGRO in vascular cells suggest an important role of GRO in the sequestration of neutrophils and multi-organ injuries induced by LPS. The guinea pig will provide an excellent model to study the roles of IL-8 and GRO, important inflammatory mediators in the human.     

Treatment of neuromuscular scoliosis with posterior-only pedicle screw fixation

Background  

To determine whether posterior-only approach using pedicle screws in neuromuscular scoliosis population adequately addresses the correction of scoliosis and maintains the correction over time.     

Pregnant adolescents living with HIV: what we know,what we need to know,where we need to go

Introduction : HIV‐infected pregnant and breastfeeding adolescents are a particularly vulnerable group that require special attention and enhanced support to achieve optimal maternal and infant outcomes. The objective of this paper is to review published evidence about antenatal care (ANC) service delivery and outcomes for HIV‐infected pregnant adolescents in low‐income country settings, identify gaps in knowledge and programme services and highlight the way forward to improve clinical outcomes of this vulnerable group. Discussion : Emerging data from programmes in sub‐Saharan Africa highlight that HIV‐infected pregnant adolescents have poorer prevention of mother‐to‐child HIV transmission (PMTCT) service outcomes, including lower PMTCT service uptake, compared to HIV‐infected pregnant adults. In addition, the limited evidence available suggests that there may be higher rates of mother‐to‐child HIV transmission among infants of HIV‐infected pregnant adolescents. Conclusions : While the reasons for the inferior outcomes among adolescents in ANC need to be further explored and addressed, there is sufficient evidence that immediate operational changes are needed to address the unique needs of this population. Such changes could include integration of adolescent‐friendly services into PMTCT settings or targeting HIV‐infected pregnant adolescents with enhanced retention and follow‐up activities.     

Application of Pharmacokinetics and Pharmacodynamics in Product Life Cycle Management. A Case Study with a Carbidopa-Levodopa Extended-Release Formulation

Increasing costs in discovering and developing new molecular entities and the continuing debate on limited company pipelines mean that pharmaceutical companies are under significant pressure to maximize the value of approved products. Life cycle management in the context of drug development comprises activities to maximize the effective life of a product. Life cycle approaches can involve new formulations, new routes of delivery, new indications or expansion of the population for whom the product is indicated, or development of combination products. Life cycle management may provide an opportunity to improve upon the current product through enhanced efficacy or reduced side effects and could expand the therapeutic market for the product. Successful life cycle management may include the potential for superior efficacy, improved tolerability, or a better prescriber or patient acceptance. Unlike generic products where bioequivalence to an innovator product may be sufficient for drug approval, life cycle management typically requires a series of studies to characterize the value of the product. This review summarizes key considerations in identifying product candidates that may be suitable for life cycle management and discusses the application of pharmacokinetics and pharmacodynamics in developing new products using a life cycle management approach. Examples and a case study to illustrate how pharmacokinetics and pharmacodynamics contributed to the selection of dosing regimens, demonstration of an improved therapeutic effect, or regulatory approval of an improved product label are presented.