Quantitation of motexafin lutetium in human plasma by liquid chromatography-tandem mass spectrometry and inductively coupled plasma-atomic emission spectroscopy

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) methods were developed and validated for the evaluation of motexafin lutetium (MLu, lutetium texaphyrin, PCI-0123) pharmacokinetics in human plasma. The LC-MS/MS method was specific for MLu, whereas the ICP-AES method measured total elemental lutetium. Both methods were fast, simple, precise, and accurate. For the LC-MS/MS method, a closely related analogue (PCI-0353) was used as the internal standard (IS). MLu and the IS were extracted from plasma by protein precipitation and injected onto and LC-MS/MS system configured with a C18 column and an electrospray interface. The lower limit of quantitation was 0.05 μg MLu mL⁻¹, with a signal-to-noise ratio of 15∶1. The response was linear from 0.05 to 5.0 μg MLu mL⁻¹. For the ICP-AES method, indium was used as the IS. The sample was digested with nitric acid, diluted, filtered, and then injected onto the ICP-AES system. Two standard curve ranges were validated to meet the expected range of sample concentrations: 0.5 to 50, and 0.1 to 10 μg Lu mL⁻¹. The LC-MS/MS and ICP-AES methods were validated to establish accuracy, precision, analyte stability, and assay robustness. Interday precision and accuracy of quality control samples were ≤6.3% coefficient of variation (CV) and within 2.2% relative error (RE) for the LC-MS/MS method, and ≤8.7% CV and within 4.9% RE for the ICP-AES method. Plasma samples from a subset of patients in a clinical study were analyzed using both methods. For a representative patient, over 90% of the elemental lutetium in plasma could be ascribed to intact MLu at early time points. This percentage decreased to 59% at 48 hours after dosing, suggesting that some degradation and/or metabolism of the drug may have occurred.     

2D:4D Digit Ratios in Adults with Gender Dysphoria: A Comparison to Their Unaffected Same-Sex Heterosexual Siblings,Cisgender Heterosexual Men,and Cisgender Heterosexual Women

Archives of Sexual Behavior - We compared gender dysphoria (GD) patients and their same-sex siblings in terms of their 2D:4D ratios, which may reflect prenatal exposure to androgen, one of the...     

Prenatal Diagnosis of Isolated Right Pulmonary Agenesis Using Sonography Alone

Pulmonary agenesis is a rare congenital anomaly, estimated to complicate around 1 per 15,000 pregnancies, in which there is complete absence or severe hypoplasia of one or both lungs, frequently associated with other abnormalities. A prospective prenatal diagnosis is a challenge, and a substantial proportion of cases are diagnosed by fetal magnetic resonance imaging, postnatal computed tomography, or postmortem. Thus, there are only a few reported cases of prenatal diagnosis in the literature. We report the prenatal diagnosis of isolated right lung agenesis diagnosed with sonography alone at a relatively early gestational age. We also present a systematic review of the literature for this condition to accompany this case study.     

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium

Background

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown.

Methods

A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function.

Results

A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible.

Conclusion

Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.     

Immunocytochemical detection of milk proteins in tracheal aspirates of ventilated infants: a pilot study

In this study, we evaluated immunocytochemical staining for milk proteins (alpha-lactalbumin and beta-lactoglobulin) in tracheal aspirates of mechanically ventilated infants, and assessed whether this staining technique supported a clinical diagnosis of aspiration in infants receiving orogastric feedings. All newborns requiring mechanical ventilation in the neonatal intensive care unit of a major tertiary care hospital were potential subjects for this study. Tracheal aspirates were obtained prior to the introduction of enteral feeding and at various time points thereafter in newborns requiring mechanical ventilation. Cells were obtained and processed for immunocytochemical staining of alpha-lactalbumin and beta-lactoglobulin. In total, 88 specimens recovered from 34 infants were adequate for staining. Alveolar macrophages recovered from most of the infants who were never fed (true negative controls) did not display immunoreactivity for milk proteins: 4/34 or 12% of infants' aspirates demonstrated presence of milk proteins before enteral feeding was commenced. Tracheal aspirates obtained from 12 infants after introduction of enteral feedings appeared to support clinical and radiological findings suggestive of aspiration events, with positive immunostaining on several occasions. These observations support our work in a murine model and demonstrate that immunocytochemical staining of tracheal aspirates for milk proteins may enhance the ability to diagnose pulmonary aspiration. Further studies are needed to define the clinical significance of our findings and the effects of single and repeated aspiration events on respiratory status.     

Intradermal radioisotope is superior to peritumoral blue dye or radioisotope in identifying breast cancer sentinel nodes

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy have emerged as the technique of choice for axillary staging of breast cancer. Several methods have been developed to identify SLNs, including peritumoral or intradermal injection of isosulfan blue dye or technetium sulfur colloid (TSC). We hypothesize that intradermal TSC is the optimal mapping technique and can be used alone to identify SLNs. STUDY DESIGN: From March 1997 through January 2001, 180 women with T1 and T2 invasive breast cancer and clinically negative axilla underwent SLN mapping and biopsy. Peritumoral TSC was injected in 74 patients, 62 of whom also received peritumoral blue dye. Intradermal TSC (above tumor) was performed in 94 patients, 76 of whom also received peritumoral blue dye. Technetium-rich nodes were identified intraoperatively using a hand-held gamma probe and blue nodes were identified visually. Hematoxylin- and eosin-stained SLN sections were examined by light microscopy for breast cancer metastases. RESULTS: Overall, the SLN mapping procedures were successful in 91% of patients. Peritumoral and intradermal TSC were successful in identifying SLNs in 78% and 97% of patients, respectively. Peritumorally injected isosulfan blue was successful in identifying 83% of SLNs. Intradermal TSC was found to be superior to peritumoral TSC and peritumoral blue dye in identifying SLNs (p = 0.00094, chi-squared, and p = 0.020, ANOVA). CONCLUSIONS: SLN mapping by intradermal TSC has a significantly higher success rate than peritumoral TSC or blue dye. There was minimal benefit in identifying additional SLNs with addition of peritumoral blue dye to intradermal TSC. So, SLN mapping and biopsy using intradermal-injected TSC can be used alone to effectively stage the axilla for breast cancer.     

Mediators of inflammation in children with type I diabetes mellitus: cytokines in type I diabetic children

Objectives: Recent evidence favors primary role of cellular autoimmunity and its humoral mediators in pathogenesis and following Type I diabetes mellitus (DM). The present study was carried out to investigate serum concentrations of C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)- in children with type I DM. Potential role of lipid metabolism, glycemic control, body mass index (BMI) and disease duration were evaluated.

Design and methods: Thirty-five children with type I DM and 30 age and gender matched nondiabetic controls were recruited for this study.

Results: Circulating IL-8 levels were elevated in children with type I DM (12.7 ± 1.7 pg/mL) compared with nondiabetic controls (5.5 ± 0.3 pg/mL) and the difference remained significant after adjustment for cofactors and covariates (p: 0.033). Although statistically insignificant serum CRP concentrations were slightly higher in diabetic children (p: 0.075). Serum TNF- and IL-6 levels were comparable in diabetic and nondiabetic groups. However newly diagnosed (<1 yr) cases had higher TNF- and IL-6 levels compared to cases with longer standing DM.

In diabetic children BMI was independently associated with an increase in serum IL-8 levels. Serum CRP, lipids, apolipoproteins and glycemic control were not significant predictors of cytokine concentrations in children with type I DM.

Conclusion: Circulating levels of IL-8 were elevated and were correlated with BMI in children with type I DM, hinting perhaps at adipose tissue as a site of production. Elevated systemic IL-6 and TNF- were limited to newly diagnosed cases suggesting activation of the inflammatory immune response system at early stages of the disease.     

Reversal of hypercalcemic acute kidney injury by treatment with intravenous bisphosphonates

We present the details of three children with hypercalcemia-induced acute kidney injury (AKI). After traditional therapy with fluids, loop diuretics, steroids and calcitonin had failed to correct the hypercalcemia, they were given treatment with low doses of intravenous (i.v.) pamidronate, which resulted in normalization of serum calcium and kidney function. In one child Doppler renal ultrasound revealed dampened arterial blood flow, which resolved with normalization of serum calcium. On the basis of cumulative data and our experience, we suggest that i.v. application of bisphosphonates be moved from the second to the first line of treatment of hypercalcemic AKI.