Journal of Investigative Medicine

Premature coronary artery disease (CAD) is a major concern in human immunodeficiency virus (HIV)-infected African Americans. The objectives of the study were to estimate the incidence of subclinical CAD, defined by the presence of coronary plaque and/or calcification on cardiac computed tomography (CT), and to identify the associated risk factors in this vulnerable population.

Between August 2003 and September 2010, 188 HIV-infected African Americans without known, or symptoms of, CAD underwent cardiac CT. The subset without demonstrable disease underwent a second cardiac CT approximately 2 years later. The incidence of disease over that period and the effects of antiretroviral treatment and other known and hypothesized risk factors were investigated.

Sixty-nine of these 188 African Americans had evidence of subclinical disease on the initial cardiac CT, confirming prior high prevalence reports. A second cardiac CT was performed on 119 African Americans without disease approximately 2 years later. The total person-years of follow-up was 284.4. Subclinical CAD was detected in 14 of these, yielding an overall incidence of 4.92/100 person-years (95% confidence interval, 2.69–8.26). Among the factors investigated, only male sex and vitamin D deficiency were independently associated with the development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, antiretroviral treatment use, or cocaine use and the incidence of subclinical CAD.

The incidence of subclinical CAD in African Americans with HIV infection is provocatively high. Larger studies are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African Americans.

High-density lipoprotein cholesterol (HDL-C) promotes cholesterol efflux from macrophage foam cells in atheroma plaques. In addition, HDL-C has anti-inflammatory and endothelium-protective properties. Despite that the only prerequisite for collateral development is shown to be the degree of coronary artery stenosis, there are significant differences even among patients with a similar degree of coronary artery disease.

We designed this study to investigate a possible association between HDL-C and coronary collateral circulation (CCC).

All study participants had at least one occluded major coronary artery. Demographic, clinical, and laboratory data were obtained from patients’ medical records. To classify CCC, we used Rentrop classification. The patients were then classified as having poor CCC (Rentrop grades 0–1) or good CCC (Rentrop grades 2–3). We performed t test and the χ² test in comparing groups and multivariate logistics regression analysis to determine the predictors of CCC. The study population consisted of 151 patients (mean age, 63.7 ± 9 years; 76.2% male).

Forty-nine patients had poor CCC and 102 patients had good CCC. The proportion of previous myocardial infarctions, serum triglycerides, and low HDL-C levels were more frequent in the poor CCC group (P = 0.026, P = 0.015, and P < 0.001, respectively). Multivariate logistic regression analysis revealed that low HDL-C is a predictor of CCC (B = 1.456; P < 0.001; odds ratio, 4.3; 95% confidence interval, 1.964–9.369).

We found that low HDL-C frequency was more frequent in the poor CCC group than the good CCC group, and HDL-C was a predictor of CCC.

Polycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance. Recently, angiopoietins were identified in the systemic circulation and have been designated angiopoietinlike proteins (ANGPTL). More recently, it is shown that angiopoietin-related growth factor (AGF, also called ANGPTL6) directly regulate lipid, glucose, and energy metabolism independent of angiogenic effects in animal studies. The aim of this study was to determine whether there is an association between AGF and PCOS.

The study included 35 patients with PCOS and 30 healthy control women. We analyzed serum levels of AGF and other biochemical and anthropometric markers in all the subjects.

This study showed that serum AGF levels were significantly higher in the subjects with PCOS (102.28 ng/mL) than those in the healthy control group (63.08 ng/mL; P < 0.001). Body mass index (24.33 vs 22.11 kg/m²; P = 0.017), free testosterone (2.81 vs 2.17 pmol/L; P = 0.009), androstenedione (3.28 vs 2.92 nmol/L; P = 0.033), 17-hydroxyprogesterone (2.72 vs 2.09 ng/mL; P = 0.039), homeostasis model of assessment-insulin resistance (2.65 vs 1.9; P = 0.016), and fasting glucose (107.09 vs 96.18 mmol/L; P = 0.001) were found significantly higher in PCOS group than in control group. But there was no correlation between AGF and these parameters in PCOS group. In addition, no correlation between the AGF and other distinctive features of PCOS was found.

Serum AGF levels were paradoxically increased in patients with PCOS in comparison with data of animal experiments. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.

Placental protein 13 (PP13) is a protein expressed only in the placenta. It is involved in gluing the placenta to the uterus and remodeling the maternal arteries to expand them. Women who subsequently develop preterm preeclampsia have low first trimester maternal serum.

The aim of this work was to assess the value of PP13 as an early marker for screening of preeclampsia and to correlate it with the PP13 messenger RNA (mRNA).

As a part of the Antenatal Screening Project, 100 women in the first trimester of pregnancy were selected and subdivided into 2 groups: 50 women who developed preeclampsia in their third trimester (patient group) and 50 women who completed normal uncomplicated pregnancy until full term (control group). Placental protein 13 level was measured using the commercially available enzyme-linked immunosorbent assay kit and PP13 mRNA was tested using reverse transcription polymerase chain reaction.

The maternal serum PP13 level in the preeclamptic group was (157.9 ± 45.5 pg/mL), which is significantly lower than that of the control group (225.3 ± 67.3 pg/mL), with highly statistically significant difference (P < 0.0001). The frequency of maternal PP13 mRNA expression was lower in the preeclamptic group (28%) compared to that in the control group (76%), with highly statistically significant difference (P < 0.0001).

Combined serum PP13 level assay and PP13 mRNA expression are reliable markers for early detection of preeclampsia, and we recommend doing it as a routine investigation during the first trimester.

Autosomal dominant tricho-rhino-phalangeal syndrome I (TRPS I) is due to mutations in the TRPS1 gene. Tricho-rhino-phalangeal syndrome I is characterized by peculiar face and skeletal anomalies. Cone-shaped epiphyses are the characteristic radiographic findings.

To describe 2 families with TRPS I and 2 novel mutations in the TRPS1 gene.

The study included 2 nonrelated families with TRPS I. All exons of the TRPS1 gene were analyzed from genomic DNA.

The TRPS1 gene mutation analysis showed in family 1 the c.978C>A nonsense mutation within exon 4 and in family 2 the c.164A>C missense mutation within exon 3.

We found 2 families with TRPS1 caused by 2 novel mutations in the TRPS gene, particularly a missense mutation in exon 3, outside the GATA zinc finger domain, that leads a mild TRPS phenotype. Our data show a higher genotypic spectrum in the TRPS I and demonstrate that mutations in the amino terminus of the transcription factor result in TRPS I syndrome.

Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 may be associated with involuntary weight loss in patients with and without cancer. However, results of previous studies have been conflicting. We evaluated patients who had involuntary weight loss to determine cytokine levels and the correlation of these cytokines with weight loss, the association with inflammation, and the potential for use in cancer diagnosis.

In 290 consecutive patients with involuntary weight loss (74 patients [26%] with cancer and 216 patients [74%] without cancer), erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were determined.

Higher ESR and levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were associated with cancer. The levels of TNF-α, IL-1β, and IL-6 did not correlate with the amount of weight loss. In multivariable analysis, only ESR was associated with cancer.

In patients with involuntary weight loss, TNF-α, IL-1β, and IL-6 were associated with cancer but were not weight loss mediators.