Papillary Thyroid Carcinoma Recurrence: Low Yield of Neck Ultrasound With an Undetectable Serum Thyroglobulin Level.

OBJECTIVES: To assess the yield of neck ultrasound (US) when serum thyroglobulin (Tg) is undetectable (<0.1 ng/mL) compared to elevated serum Tg in patients with differentiated papillary thyroid carcinoma (PTC) treated with thyroidectomy and radioactive iodine 131 (RAI) ablation. METHODS: A retrospective chart review was conducted from 2010 through 2015 at an academic institution evaluating US results in patients with serum Tg levels obtained within 6 months of a neck US examination after thyroidectomy and RAI. The reference standard for recurrence was pathologic results from US-guided fine-needle aspiration (FNA) or follow-up for at least 1 year. RESULTS: Among 76 patients with undetectable serum Tg levels, there were 19 examinations in 18 patients in which US raised the possibility of recurrence. None of these 18 patients had recurrence by FNA (n = 8) or clinical follow-up of at least 1 year (n = 10). Among 65 patients with elevated serum Tg levels, there were 24 examinations in 22 patients in which US raised the possibility of recurrence. Twelve patients underwent FNA, with 9 patients (34.6%) showing PTC; 7 patients had follow-up neck US examinations showing stability of findings; and 3 patients were lost to follow up. The yield of neck US was significantly lower when serum Tg was undetectable compared to when levels were elevated (P = .001). CONCLUSIONS: Neck US did not identify recurrent PTC when the serum Tg level was undetectable in patients who underwent total thyroidectomy and RAI therapy. Eliminating neck US when serum TG levels are undetectable could decrease unnecessary imaging examinations without negatively affecting the ability to detect recurrent disease.

Unenhanced MRI as an Alternative to 99mTc-Labeled Dimercaptosuccinic Acid Scintigraphy in the Detection of Pediatric Renal Scarring.

OBJECTIVE: The purpose of this study was to determine whether unenhanced MRI without sedation is a feasible substitute for dimercaptosuccinic acid (DMSA) scintigraphy in the detection of renal scars in pediatric patients. SUBJECTS AND METHODS: Patients scheduled for 99mTc-labeled DMSA scintigraphy for assessment of possible renal scars were recruited to undergo unenhanced MRI (free-breathing fat-suppressed T2-weighted single-shot turbo spin-echo and T1-weighted gradient-echo imaging, 13 minutes' total imaging time). Scintigraphic and MRI studies were evaluated by two independent blinded specialty-based radiologists. For each imaging examination, readers identified scars in upper, middle, and lower kidney zones and rated their diagnostic confidence and the quality of each study. The scintigraphic readers' consensus score opinion for the presence of scars was considered the reference standard. RESULTS: DMSA scintigraphy showed scarring in 19 of the 78 (24.4%) evaluated zones and MRI in 18 of the 78 (23.1%). The two MRI readers found mean sensitivities of 94.7% and 89.5%, identical specificities of 100%, and diagnostic accuracies of 98.7% and 97.4%. Interobserver agreement was 98.7% for MRI and 92.3% for DMSA scintigraphy. The MRI readers were significantly more confident in determining the absence rather than the presence of scars (p = 0.02). MRI readers were more likely to rate study quality as excellent (84.6%) than were the scintigraphic readers (57.7%) (p = 0.024). CONCLUSION: Unenhanced MRI has excellent sensitivity, specificity, diagnostic accuracy, and interobserver agreement for detecting renal scars in older children who do not need sedation. It may serve as a substitute modality, especially when DMSA is not available.

Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408). METHODS: Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects. RESULTS: N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed. CONCLUSION: N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.

Manual therapy directed at the knee or lumbopelvic region does not influence quadriceps spinal reflex excitability.

UNLABELLED: Manual therapies, directed to the knee and lumbopelvic region, have demonstrated the ability to improve neuromuscular quadriceps function in individuals with knee pathology. It remains unknown if manual therapies may alter impaired spinal reflex excitability, thus identifying a potential mechanism in which manual therapy may improve neuromuscular function following knee injury. AIM: To determine the effect of local and distant mobilisation/manipulation interventions on quadriceps spinal reflex excitability. METHODS: Seventy-five individuals with a history of knee joint injury and current quadriceps inhibition volunteered for this study. Participants were randomised to one of five intervention groups: lumbopelvic manipulation (grade V), lumbopelvic manipulation positioning (no thrust), grade IV patellar mobilisation, grade I patellar mobilisation, and control (no treatment). Changes in spinal reflex excitability were quantified by assessing the Hoffmann reflex (H-reflex), presynaptic, and postsynaptic excitability. A hierarchical linear-mixed model for repeated measures was performed to compare changes in outcome variables between groups over time (pre, post 0, 30, 60, 90 min). RESULTS: There were no significant differences in H-reflex, presynaptic, or postsynaptic excitability between groups across time. CONCLUSIONS: Manual therapies directed to the knee or lumbopelvic region did not acutely change quadriceps spinal reflex excitability. Although manual therapies may improve impairments and functional outcomes the underlying mechanism does not appear to be related to changes in spinal reflex excitability.

True and sham acupuncture produced similar frequency of ovulation and improved LH to FSH ratios in women with polycystic ovary syndrome.

CONTEXT: Acupuncture may represent a nonpharmaceutical treatment for women with polycystic ovary syndrome (PCOS), based on four studies. OBJECTIVE: The objective of the study was to determine whether true, as compared with sham, acupuncture normalizes pituitary gonadotropin hormones and increases ovulatory frequency in women with PCOS. DESIGN: This was a randomized, double-blind, sham-controlled clinical trial (5 month protocol). SETTING: The study was conducted in central Virginia. PARTICIPANTS: Eighty-four reproductive-aged women completed the intervention. Eligibility required a PCOS diagnosis and no hormonal intervention 60 d before enrollment. INTERVENTIONS: Intervention included 12 sessions of true or sham acupuncture (Park sham device) for 8 wk. MAIN OUTCOME MEASURES: Serum LH and FSH at baseline, after intervention, and 3 months later were measured. Ovulation was measured with weekly urine or blood samples. RESULTS: Both arms demonstrated a similar mean ovulation rate over the 5 months (0.37/month among n = 40 true acupuncture and 0.40/month among n = 44 sham participants, P = 0.6), similar LH to FSH ratio improvement (-0.5 and -0.8 true and sham, respectively, P < 0.04 after intervention vs. baseline) and a similar decline in LH over the 5-month protocol (P < 0.05). Neither arm experienced a change in FSH. There were seven pregnancies (no difference by intervention, P = 0.7). Lower fasting insulin and free testosterone were highly correlated with a higher ovulation rate within the true acupuncture group only (P = 0.03), controlling for prestudy menstrual frequency and body mass index. CONCLUSION: We were unable to discern a difference between the true and sham acupuncture protocols for these women with PCOS, and both groups had a similar improvement in their LH/FSH ratio.

Effects of carbohydrate supplementation on the RPE-blood lactate relationship.

PURPOSE: To examine the effects of carbohydrate (CHO) ingestion on the RPE-blood lactate relationship during incremental and constant-effort exercise. METHODS: Six male and three female subjects (mean age = 27.2 +/- 8.2 yr, height [ht] = 174.5 +/- 13.5 cm, weight [wt] = 68.9 +/- 12.5 kg, body fat = 18.5 +/- 8.3%), completed two incremental cycling lactate threshold (LT)/(.)VO2peak tests followed by two 45-min production trials. Two hundred and forty milliliters of either carbohydrate or placebo (PL) was ingested before and every 15 min during exercise. RESULTS: No differences were observed between conditions at LT, 2.5 and 4.0 mM, and peak. Within the CHO condition: V O2 = 25.0, 32.6, 37.5, 47.2 mL x kg x min(-1); power output = 123.3, 170.7, 200.1, 241.7 W; RPE = 12.8, 15.4, 17.2, 19.3; and HR = 137.4, 156.8, 168.7, 187.7 beats x min(-1) at LT, 2.5 mM, 4.0 mM, and peak, respectively. Within PL: V O2 = 24.7, 32.5, 36.8, 45.7 mL x kg x min(-1); power output = 130.0, 175.4, 201.9, 240.0 W; RPE = 12.1, 15.0, 17.0, 19.3; and HR = 134.9, 157.9, 169.6, 187.2 beats x min(-1), respectively. In the CHO condition, blood glucose was higher (P < 0.001), and a trend was observed for lower RPE over time (P = 0.07). During the production trials (RPE of 16) in the CHO condition, higher blood glucose area under the curve (AUC) (PL: 204.1 +/- 79.3 mM; CHO: 220.6 +/- 18.5 mM; P = 0.039) and a trend for greater total work (PL: 448.5 +/- 73.8 kJ; CHO: 470.5 +/- 65.6 kJ; P = 0.089) were observed. CONCLUSIONS: We conclude that 1) CHO ingestion does not alter the blood lactate-RPE relationship during incremental LT/(.)VO2peak cycling; and 2) carbohydrate supplementation during exercise, eliciting high RPE, may increase work output during training sessions.

Effects of dietary supplementation with conjugated linoleic acid on experimental human rhinovirus infection and illness.

BACKGROUND: Because studies suggest that the dietary supplement conjugated linoleic acid (CLA) has immunomodulatory activities that might benefit common colds, we performed two studies of CLA effects in experimental human rhinovirus (HRV) infection. METHODS: The first study explored whether CLA supplementation (Safflorin; Loders Croklaan, BV, Wormerveer, the Netherlands) altered the virological or clinical course of experimental HRV infection, and the second explored whether CLA affected the frequency and severity of HRV cold-associated sore throat and cough. The trials were randomized, double-blinded and placebo-controlled. In total, 50 healthy volunteers aged 18-45 years and susceptible to HRV type-39 (serum neutralizing antibody titre < or = 1:2) participated in study 1 and 80 similar volunteers susceptible to Hank's HRV participated in study 2. Participants ingested CLA 2 g/day or placebo for 4 weeks before and 4 days following intranasal HRV inoculation. The primary endpoint for study 1 was the frequency of colds and for study 2 was the symptom severity scores for sore throat and cough. RESULTS: In study 1, 10/24 (42%) placebo compared with 7/21 (33%) CLA participants developed colds (P = 0.53). CLA was associated with significant reductions in mean scores for cough (0 CLA versus 0.9 placebo) and sore throat (0.8 CLA versus 2.9 placebo). In study 2, clinical colds developed in 19/33 (58%) placebo and 27/43 (63%) CLA participants. Symptom scores for cough (0.9 CLA versus 1.0 placebo) and sore throat (2.6 CLA versus 3.2 placebo) were not significantly different. Similarly no differences in nasal viral titres or serological responses were found. CONCLUSIONS: CLA dietary supplementation had no consistent effects on the virological or clinical course of experimental HRV colds. A larger study would be required to detect more subtle effects of CLA on HRV cold-associated symptoms.

Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight.

OBJECTIVES: We tested the hypothesis that twice weekly prophylactic dosing of fluconazole prevents invasive candidiasis without promoting resistant Candida species in high-risk, preterm infants. STUDY DESIGN: We compared our previous dosing schedule (Group A) to a less frequent dosing schedule of twice a week (Group B) of fluconazole prophylaxis for up to 6 weeks in a prospective, randomized, double-blind clinical trial in preterm infants weighing <1000 grams at birth and with an endotracheal tube and/or central vascular catheter over a 24-month period. Weekly surveillance cultures were obtained on study patients. RESULTS: Candida colonization was documented in 5 (12%) of 41 Group A and in 4 (10%) of 40 Group B infants. Candida sepsis developed in two (5%) of Group A and one (3%) of Group B infants (risk difference, -0.02; 95% confidence interval, -0.14-0.10; P=.68). All fungal isolates remained sensitive to fluconazole, and no drug side effects were documented. CONCLUSIONS: Twice weekly dosing of prophylactic fluconazole can decrease Candida colonization and invasive infection, cost, and patient exposure in high-risk, preterm infants weighing <1000 grams at birth. We speculate that lower and less frequent dosing may delay or prevent the emergence of antifungal resistance.

Magnesium deficiency is associated with insulin resistance in obese children.

OBJECTIVE: Magnesium deficiency has been associated with insulin resistance (IR) and increased risk for type 2 diabetes in adults. This study was designed to determine whether obese children exhibit serum or dietary magnesium deficiency and its potential association with IR. RESEARCH DESIGN AND METHODS: We studied 24 obese nondiabetic children (BMI > or =85th percentile) and 24 sex- and puberty-matched lean control subjects (BMI <85th percentile). We measured serum magnesium, indexes of insulin sensitivity, dietary magnesium intake (using a food frequency questionnaire), and body composition (by air displacement plethysmography). RESULTS: Serum magnesium was significantly lower in obese children (0.748 +/- 0.015 mmol/l, means +/- SE) compared with lean children (0.801 +/- 0.012 mmol/l) (P = 0.009). Serum magnesium was inversely correlated with fasting insulin (r(s) = -0.36 [95% CI -0.59 to -0.08]; P = 0.011) and positively correlated with quantitative insulin sensitivity check index (QUICKI) (0.35 [0.06-0.58]; P = 0.015). Dietary magnesium intake was significantly lower in obese children (obese: 0.12 +/- 0.004 vs. lean: 0.14 +/- 0.004 mg/kcal; P = 0.003). Dietary magnesium intake was inversely associated with fasting insulin (-0.43 [-0.64 to -0.16]; P = 0.002) and directly correlated with QUICKI (0.43 [0.16-0.64]; P = 0.002). CONCLUSIONS: The association between magnesium deficiency and IR is present during childhood. Serum magnesium deficiency in obese children may be secondary to decreased dietary magnesium intake. Magnesium supplementation or increased intake of magnesium-rich foods may be an important tool in the prevention of type 2 diabetes in obese children.

Sustained growth hormone (GH) and insulin-like growth factor I responses to prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged and older men.

Postulated mechanisms underlying the relative hyposomato-tropism of aging include reduced hypothalamic drive by GHRH. To test this notion, we administered 1 mg (n = 11) vs. 4 mg (n = 11) recombinant human GHRH-1,44-amide s.c. twice daily for 3 months in a double-blind, parallel-cohort design to 22 healthy men (ages, 53-68 yr). After 3 months, GHRH elevated: overnight GH concentrations from 0.71 +/- 0.19 to 1.74 +/- 0.39 microg/liter (P < 0.001; 1 mg) and from 0.80 +/- 0.15 to 5.12 +/- 0.40 microg/liter (P < 0.001; 4 mg) and IGF-I concentrations from 117 +/- 14 to 234 +/- 20 microg/liter (P = 0.007; 1 mg) and from 147 +/- 13 to 286 +/- 22 microg/liter (P < 0.001; 4 mg). Only the higher GHRH dose also increased total body water (tritium space; P = 0.024) and fat-free mass (dual-energy x-ray absorptiometry; P = 0.021), and reduced total abdominal adiposity (computed axial tomography scan; P = 0.042). Both supplementation schedules shortened the time required to walk 30 m and ascend four flights of stairs (P < 0.025 each). Lower extremity strength, aerobic capacity, and bone mineral density did not change. Local injection site reactions were common. We conclude that sc administration of a large dose of GHRH (4 mg) twice daily for 3 months elevates GH and IGF-I concentrations, increases total body water and fat-free mass, reduces total abdominal adiposity, and enhances certain performance measures in healthy aging men but causes local skin reactions.

Estradiol supplementation in postmenopausal women doubles rebound-like release of growth hormone (GH) triggered by sequential infusion and withdrawal of somatostatin: evidence that estrogen facilitates endogenous GH-releasing hormone drive.

We postulated that short-term estradiol replacement in postmenopausal women may act, in part, by facilitating endogenous GHRH release or action. A prediction of this hypothesis is that estradiol repletion should enhance postsomatostatin rebound GH secretion, which appears to be driven by hypothalamic outflow of GHRH. To this end, we administered placebo and estradiol to eight healthy estrogen-withdrawn postmenopausal volunteers in a prospectively randomized, patient-blinded, within-subject crossover design for a total of 36 d. Rebound release of GH was assessed between d 7 and 36 of intervention on separate randomly ordered mornings after continuous iv infusion of saline or somatostatin (9 micro g/kg.h for 3 h). Secretion was quantitated by frequent (10-min) blood sampling for 7 h, GH chemiluminescence assay, and deconvolution analysis. Compared with placebo, estradiol replacement: 1) stimulated spontaneous pulsatile GH secretion by 3.5-fold (95% confidence interval, 2.1- to 5.6-fold) (P < 0.001); and 2) amplified the mass of GH secreted in response to abrupt somatostatin withdrawal by 2.1-fold (95% confidence interval, 1.3- to 3.4-fold) (P = 0.003). Estrogenic augmentation of rebound-like GH secretion was specific, because the pharmacological effects of exogenous GHRH (1 micro g/kg) and GH-releasing peptide-2 (1 micro g/kg, a synthetic ghrelin analog) were not affected. In summary, short-term supplementation with estradiol in postmenopausal individuals doubles the mass of rebound-like GH secretion induced by abrupt somatostatin withdrawal without modifying stimulation by a pharmacological dose of GHRH or GH-releasing peptide-2. Accordingly, we hypothesize that estradiol stimulates pulsatile GH secretion, at least in part, by enhancing the release and/or action of hypothalamic GHRH.