Journal of Investigative Medicine

The objective of this study was to determine whether dynamic magnetic resonance imaging (dMRI) enhancement parameters could predict dopamine agonist (DA) resistance in prolactinomas.

We retrospectively identified patients with prolactinomas who were treated with DA and underwent dMRI from 2001 through 2012 at Mayo Clinic (Rochester, MN). Intensities of the adenoma and pituitary gland were measured by drawing regions of interest on the images. Enhancement ratio, enhancement peak, prepeak slope (PPS), and enhancement time were compared between DA-resistant and DA-responsive groups, between DA-treated and DA-naive groups, and between the first and follow-up dMRIs.

We identified 49 patients with prolactinomas, with 6 (12.2%) showing DA resistance. Thirty-seven patients (75.5%) underwent dMRI while receiving treatment, 12 (25.5%) underwent dMRI before starting therapy, and 10 (20.4%) had follow-up dMRI after DA therapy. The PPS of the tumor was higher in the treatment-resistant group versus the responsive group (mean [SD], 4.42 [3.19] vs 2.65 [1.59]; P = 0.03), whereas no difference was noted in the pituitary gland (5.79 [2.21] vs 4.06 [2.48]; P = 0.11). Logistic regression analysis indicated that tumor PPS was associated with DA resistance (odds ratio, 1.71; 95% confidence interval, 1.07–3.27; P = 0.02).

Dynamic MRI with PPS analysis potentially can be used early in the treatment course to evaluate DA resistance in pituitary prolactinomas.

Hyperhomocysteinemia and hyperuricemia are both considered risk factors for coronary artery disease. However, the relationship between the 2 has not yet been thoroughly investigated. This study aimed to evaluate this relationship more closely.

This study is a retrospective cross-sectional analysis of data from a screening center in Israel assessing 16,477 subjects, within an age range of 20 to 80 years.

The mean age of the study sample was 46 years, and 68% were males. Hyperuricemia was found in 24.9% and 14.6% of subjects with elevated and normal homocysteine serum levels, respectively (P < 0.001). A positive association was found between homocysteine serum levels and uric acid serum levels. Compared with subjects with normal homocysteine serum levels, those with hyperhomocysteinemia had an odds ratio (OR) for hyperuricemia of 1.7 (95% confidence interval [CI], 1.5–1.9) and 1.6 (95% CI, 1.1–2.5) for males and females, respectively. After multivariate adjustment for age, hypertension, body mass index, estimated glomerular filtration rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and thiazide use, the association remained significant in males (OR, 1.5; 95% CI, 1.3–1.7; P < 0.001) but not in females (OR, 0.9; 95% CI, 0.6–1.6; P = 0.82).

This large cohort showed a significant association between hyperhomocysteinemia and hyperuricemia. Sex differences were observed. This study suggests that accelerated atherosclerosis may be a consequence of the combined effect of these 2 factors.

Parathyroid hormone (PTH) measurements in hemodialysis (HD) patients are routinely performed every 3 to 6 months of therapy, which are adjusted in accordance with PTH. However, recent evidences show very high PTH biological variability. The aim of our study was to evaluate the role of serum β-crosslap (CTX), a validated marker of bone resorption, as indicator of PTH maintenance at different time intervals.

Forty-six HD patients fulfilled the inclusion criteria (HD age of more than 21 months and 7 PTH measurements for the last 21 months) for this retrospective cohort study and were enrolled. Data of the backward quarter PTH values for the last 21 months were collected from clinical records, and a single CTX was measured.

To evaluate the relationship between CTX value and the maintenance of PTH in the short-term and long-term, 7 time intervals (3, 6, 9, 12, 15, 18, and 21 months) were stated and the mean value of PTH was measured within each interval and calculated for every patient.

We found the following: (1) positive correlation between mean PTH in each time interval and β-crosslaps with a progressive increase of the correlation coefficient (highest value for the 12- and 21-month intervals); (2) significant differences between tertiles of β-crosslaps at 6-, 9-, 12-, 15-, 18-, and 21-month intervals, with a progressively growing value of the test coefficient; and (3) after the computation of receiver operating characteristic curves, β-crosslaps showed to significantly estimate threshold PTH values with the highest areas under the curves (AUCs; AUC, 0.763; 95% confidence interval, 0.625–0.901 for <150 pg/mL of PTH; AUC, 0.774; 95% confidence interval, 0.614–0.934 for >300 pg/mL of PTH) and best value of both sensitivity and specificity at the 12-month time interval (82% and 72% for <150 pg/mL of PTH; 78% and 79% for >300 pg/mL of PTH).

In HD patients, β-crosslaps have a potential ability to best estimate backward PTH into 12 months of interval.

CCL13, a recently identified CC chemokine, plays an important role in the process of joint destruction, which is considered a common cause for osteoarthritis (OA). This study aims to examine the relation of CCL13 levels in serum and synovial fluid (SF) with the radiographic severity of OA.

CCL13 levels in serum and SF were evaluated using enzyme-linked immunosorbent assay method in 240 patients with knee OA and 134 control subjects. The progression of OA was classified using the Kellgren-Lawrence (KL) system by evaluating x-ray changes observed in anteroposterior knee radiography.

Knee OA patients had higher levels of serum CCL13 compared with control subjects. Knee OA patients with KL grade 4 showed significantly elevated CCL13 levels in serum and SF compared with those with KL grades 2 and 3. Knee OA patients with KL grade 3 had significantly higher SF levels of CCL13 compared with those with KL grade 2. CCL13 levels in serum and SF of knee OA patients were significantly correlated with disease severity evaluated by KL grading criteria.

CCL13 levels in serum and SF were correlated with the radiographic severity of OA. CCL13 levels in serum and SF may serve as a biomarker for the progression of OA.

Previous studies have shown association of the multifunctional hepatic protein α2HS-glycoprotein/human fetuin A with insulin resistance, type 2 diabetes mellitus, metabolic syndrome, obesity, and atherosclerosis. Reports of contribution of α2HS-glycoprotein/human fetuin A rs4917 single-nucleotide polymorphism to the development of these pathologic processes are inconsistent. We aimed to investigate the association between variants of rs4917 and parameters of obesity, lipid status, the proinflammatory cytokine tumor necrosis factor α (TNF-α), adipokines (adiponectin, resistin), and insulin resistance in 2 cohorts.

Eighty-one healthy persons (cohort 1) and 157 patients with previous myocardial infarction (cohort 2) were included in this cross-sectional study. rs4917 Polymorphism was determined by the allele-specific KASP by design genotyping assays.

In cohort 1, T-nucleotide carriers had lower low-density lipoprotein cholesterol levels compared with non-T carriers. The serum concentration of TNF-α was found to be higher carrying the non-T allele in cohort 1; however, this difference was not observed in cohort 2. In cohort 2, T carriers had lower body mass index and abdominal and waist circumferences than did non-T carriers. The T nucleotide was more frequent in nonobese than in obese patients (χ² = 5.217, P = 0.022). Nonobese, nondiabetic T carriers still had lower body mass index and waist circumference than did non-T carriers.

Our data suggest that the T nucleotide in rs4917 is associated with more favorable lipid status among healthy persons (i.e., lower low-density lipoprotein cholesterol) and anthropologic parameters of obesity in cohort 2. The protective role of the T allele may also be associated with lower TNF-α levels found in healthy individuals.

Ciliopathies refer to a wide variety of diseases in which mutations in the genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia play pathogenetic roles, and in such diseases, retinal involvement may be present. Nitric oxide (NO) plays an important role in airway physiology, including regulation of ciliary motility and host defense. In primary ciliary dyskinesia, a syndromic ciliopathy, nasal NO (nNO) levels were reported to be extremely low compared with controls, possibly reflecting molecular defects leading to structural and functional ciliary abnormalities. We investigated whether decreased nitric levels were also present in patients with retinal inherited dystrophies.

Nasal NO was measured in a group of patients with syndromic and nonsyndromic inherited retinal dystrophies.

Patients with inherited retinal dystrophies, both syndromic and nonsyndromic, had mean nNO levels that were lower than healthy controls. Seven patients had particularly low levels of nNO: 3 patients with retinitis pigmentosa and 4 individual patients with Mainzer-Saldino syndrome, Bardet-Biedl syndrome, Usher syndrome, and cone-rod disease.

These findings provide evidence that there is an underlying abnormal ciliary function involving the nasal epithelium in some patients with inherited retinal dystrophies.