Insights from a thermography-based method suggesting higher carotid inflammation in patients with diabetes mellitus and coronary artery disease.

AIM: Diabetes mellitus (DM) is an independent risk factor for stroke. In a DM population, carotid atheromatosis is a major cause of stroke. The role of carotid plaque inflammation remains conflicting. Microwave radiometry (MWR) is a new non-invasive method allowing in vivo measurement of the temperature of tissues, so reflecting inflammation. The aim of this prospective study was to evaluate the impact of DM on carotid artery inflammation in patients with documented coronary artery disease (CAD). METHODS: Consecutive patients (n=300) with significant CAD were evaluated by: (1) ultrasound study of both carotid arteries; and (2) the temperature difference (ΔT) along each carotid artery on MWR. ΔT ≥ 0.90 °C was considered high ΔT. Vessel- and patient-based analyses were performed to determine the impact of DM on morphological and functional characteristics of carotid arteries. RESULTS: Out of 300 patients, 113 (37.7%) had DM. Patients with DM had similar carotid plaque thickness compared with patients without DM in both vessel- and patient-based analyses. In contrast, patients with DM exhibited higher ΔT values in both vessel- and patient-based analyses. On multivariate logistic regression analysis, DM was an independent predictor of high ΔT both unilaterally and bilaterally (OR: 1.66, 95% CI: 1.06-2.58, P=0.03 and OR: 1.96, 95% CI: 1.01-3.81, P=0.05, respectively). CONCLUSION: In patients with CAD, DM was an independent predictor of local carotid plaque inflammatory activation. Whether or not the assessment of functional plaque characteristics by MWR can be an additional prognostic tool independent of structural factors now needs to be further investigated.

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention.

BACKGROUND: The majority of cardiovascular events in patients undergoing PCI arise from the progression of NCL during the long-term follow-up period. The purpose of the study was to investigate the clinical and angiographic factors related to the progression of non-culprit lesions (NCL) of patients undergoing percutaneous coronary interventions (PCI). METHODS: One hundred and seventeen patients that underwent two coronary angiograms with a time interval greater than 3 months were enrolled. All patients underwent PCI as a treatment for the culprit lesion. In the second coronary angiography we investigated whether they had a new culprit lesion clearly differentiated from the one of the first angiogram. The demographic characteristics, the clinical syndrome responsible for the first PCI and the procedural characteristics were recorded. Quantitative coronary angiography was performed at the culprit lesion of the second angiography and in the same lesion in the first angiography. RESULTS: Multivariate analysis showed that the independent variables for the development of a significant lesion at the follow-up requiring intervention were: the presence of complex lesion (53.78% vs 36.22%, p<0.001, OR=39.42), acute myocardial infarction (AMI) at the initial diagnosis (36.3% vs 32.4%, p<0.001, OR=3.9), and smoking (46.15% vs 53.84%, p=0.03, OR=0.29). CONCLUSIONS: Patients with AMI and complex morphology of NCL have increased risk for a new intervention after successful PCI. Smoking at the time of the follow up, was associated with fewer coronary interventions.

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: implications for systemic inflammation.

AIMS: Local coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation. METHODS: We included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (DeltaT) between the lesion and proximal vessel wall. RESULTS: We included 104 (n=208 lesions) patients: 32 (n=64 lesions) had DM and 72 (n=144 lesions) were non-DM (control group). DeltaT was increased in DM in both CLs and NCLs (CLs: DM=0.12+/-0.06 degrees C; no DM=0.06+/-0.04 degrees C; P<0.01 versus NCLs: DM=0.13+/-0.08 degrees C versus no DM=0.06+/-0.05 degrees C; P<0.01). Patients with DM had similar DeltaT in CLs and NCLs (P=0.49). A linear correlation was detected between heat production in all lesions and CRP (R=0.45; P<0.01), which was attributed to the correlation of DeltaT in lesions of patients with DM and CRP (R=0.32; P<0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high DeltaT in one or both lesions (P<0.01). CONCLUSION: In patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.

Increased coronary sinus blood temperature: correlation with systemic inflammation.

BACKGROUND: Recent studies have shown that patients with single vessel coronary artery disease (CAD) suffering from acute coronary syndromes (ACS) have increased coronary sinus (CS) blood temperature compared with the right atrium (RA). The aim of this study was to investigate whether there is a correlation between systemic inflammatory indexes and CS temperature and whether there is a difference in CS temperature between patients with single vs. multivessel disease. MATERIALS AND METHODS We included consecutive patients scheduled for coronary angiography for recent-onset chest pain evaluation. We measured C-reactive protein (CRP) levels in the study population. Coronary sinus and RA blood temperature measurements were performed by a 7F thermography catheter. DeltaTau was calculated by subtracting the RA from the CS blood temperature. RESULTS: The study population comprised 53 patients with ACS, 25 patients with stable angina (SA) and 22 subjects without CAD (control group). DeltaTau was greater in patients with ACS and with SA compared with the control group (0.22 +/- 0.10 degrees C, 0.18 +/- 0.04 degrees C vs. 0.14 +/- 0.07 degrees C, P < 0.01 for both comparisons). The ACS group had greater DeltaTau compared with the SA group, although the difference did not reach statistical significance (P = 0.09). Eighteen (39.1%) out of 46 patients with multivessel disease had three-vessel disease and 28 (60.8%) had two-vessel disease. DeltaTau between patients with multivessel and single vessel disease was similar (0.22 +/- 0.01 degrees C, 0.19 +/- 0.01 degrees C, P = 0.17). The levels of CRP were well correlated with DeltaTau (R = 0.35b, P < 0.01). CONCLUSIONS: Systemic inflammation is well correlated with CS temperature; thus, an inflammatory process could be the underlying mechanism for increased heat production from the myocardium.

Hepatocyte function during experimental use of a bioartificial liver.

The aim of the present study was to compare the function of fresh versus cryopreserved hepatocytes in an experimental bioartificial liver system (BAL), especially designed to reproduce clinical parameters. Our BAL consists of a pump, a plasma reservoir, a membrane oxygenator, and a hollow fiber module loaded with 5 x 10(9) isolated porcine hepatocytes, either fresh (n = 5) or cryopreserved (n = 5). In the present setting, the system was isolated and perfused for 6 hours with recirculating plasma obtained from pigs with ischemic liver failure (toxic plasma). The following parameters were studied at 0 and 6 hours: oxygen consumption by the hepatocytes in the bioreactor, hepatocyte viability, as well as plasma concentrations of AST, LDH, ammonia, urea, and total bilirubin. MEGX concentrations were measured following injection of lidocaine into the system 30 minutes after initiation of plasma recirculation. Compared to cryopreserved cells, fresh hepatocytes showed higher viability at both time points studied (P <.05). Furthermore, during BAL sessions, ammonia levels were reduced while urea, AST, and LDH levels were increased with both preservation types (P <.05). Total bilirubin levels increased only during sessions with cryopreserved hepatocytes. After lidocaine administration, both fresh and cryopreserved hepatocytes were capable of producing MEGX; however, fresh-cell bioreactors produced significantly more MEGX at both 30 and 60 minutes after lidocaine administration. Oxygen consumption was significantly higher by fresh-cell bioreactors both before and after BAL use. In conclusion, hepatocytes in the BAL bioreactor showed preservation of important metabolic functions, when perfused with homologous toxic plasma. Fresh cells appeared to respond better than did cryopreserved ones.

Auxologic data and hormonal profile in long-term survivors of childhood acute lymphoid leukemia.

PURPOSE: Eighty patients, 50 girls and 30 boys 13.5 +/- 4.09 years of age, on continuous first remission, were evaluated 7.9 +/- 3.2 years after the diagnosis of acute lymphoid leukemia (ALL). PATIENTS, METHODS AND RESULTS: All patients were treated according to current protocols. Cranial irradiation dose was 1,800 rad in 10 fractions for 50 patients, and 2,400 rad in 18 fractions for the remaining 30. The mean percentile and SDS for height were 42.5 +/- 26 and -0.3 +/- 1.1 for boys, and 37.8 +/- 15.3 and -0.54 +/- 0.9 for girls, respectively. The final height and the corresponding SDS was 171 +/- 5.75 cm and -0.35 +/- 0.8 for boys, and 158 +/- 7.1 cm and -0.89 +/- 1.1 for girls, respectively. Using skin fold thickness, obesity was observed in a high percentage of patients. The head circumference (HC) percentile was 36.8 +/- 24 for boys and 40.9 +/- 29 for girls, and was even lower (30.96 +/- 25.5) for those who received a radiation dose of 2,400 rad. Menarche was earlier in girls with ALL than in normal girls (11.6 +/- 1.5 vs. 12.4 +/- 1.02 years). Testicular size was within normal limits, except in three boys whose size was at or below the third percentile. In two of them, testes had been irradiated. The mean thyroxin, thyroid-stimulating hormone, and prolactin values were within normal limits (8.6 +/- 2 micrograms/dl, 2.6 +/- 1.1 microU/dl, and 5.9 +/- 4.8 ng/ml, respectively). The somatomedin-C values for patients in the prepubertal stage were 1.49 +/- 0.85 versus 0.96 +/- 0.6 in the controls (p < 0.05), whereas for patients in the pubertal stage they were 1.92 +/- 1 versus 1.88 +/- 1 in the controls. The sex steroid and dehydroepiandrosterone sulfate values were within normal limits. In a high percentage of children, follicle-stimulating hormone and luteinizing hormone values were above the normal range for their age, sex, and pubertal stage. The mean glycosylated hemoglobin values were normal. CONCLUSIONS: 1. Linear growth, although impaired in the group as a whole, is within the normal range for the majority of children with ALL. A small percentage of children have significantly impaired growth, and must be identified early and receive appropriate therapy. 2. Obesity is more frequently present in patients with ALL. 3. HC is lower than expected, indicating impaired brain growth, which is worse in children irradiated with 2,400 rad. 4. Menarche is earlier and the gonadotrophin level is higher than normal, suggestive of either hypothalamic dysfunction, subtle ovarian failure, or both.

Familial hypothyroidism caused by a nonsense mutation in the thyroid-stimulating hormone beta-subunit gene.

Hereditary hypothyroidism caused by thyroid-stimulating hormone (TSH) deficiency is a rare autosomal recessive disease. Affected individuals show symptoms of severe mental and growth retardation that can be prevented by early administration of exogenous thyroid hormone. In this paper, we describe two related Greek families with three children affected by congenital TSH-deficient hypothyroidism. Sequence analysis of the TSH beta-subunit gene (TSHB) showed that the mutation responsible for the hypothyroidism in these families is a nonsense mutation in exon 2. This mutation is a G-to-T transversion at nucleotide 94 that destroys the only TaqI site in the TSHB-coding region and gives rise to a novel 8.5-kb TaqI fragment. Restriction analysis showed that the three affected children are homozygous for the 8.5-kb allele and that the four parents and two unaffected children are heterozygous. This mutation gives rise to a truncated peptide which includes only the first 11 of 118 amino acids of the mature TSHB peptide.

Ichthyosis and hypogonadism in two brothers with deletion of the short arm of the X chromosome.

Two brothers were examined because of ichthyosis and hypogonadism. Their testes were small. There was no response of plasma testosterone to human chorionic gonadotropin and no response of plasma luteinizing hormone and follicle-stimulating hormone to intravenous luteinizing-hormone-releasing hormone. They both had hyposmia. Steroid sulfatase activity in white blood cells was zero. Flow cytometry and the use of special probes indicated that these two brothers had a large deletion of the short arm of the X chromosome which included the STS locus, the closely linked locus DXS237 and probably the gene for hypogonadism, findings which offer the opportunity for speculations on the locus of control of normal testicular development and function.