Common carotid intima-media thickness in growth hormone (GH)-deficient adolescents: a prospective study after GH withdrawal and restarting GH replacement

We prospectively investigated the risk of early atherosclerosis, by classical cardiovascular risk factors and intima-media thickness (IMT) at the common carotid arteries, in 23 adolescents diagnosed as GH deficient (GHD) during childhood and in 23 healthy sex-, age-, and BMI-matched controls. Measurements were performed in all subjects before stopping GH replacement. Because the diagnosis of GHD had been confirmed in 15 of the 23 adolescents, the protocol changed according to the diagnosis as follows: measurements were repeated after 6 months of GH withdrawal and 6 months of GH reinstitution in the 15 with GHD, and after 6 and 12 months of GH withdrawal, measurements were also taken in the eight non-GHD subjects. Serum IGF-I levels were in the normal range for age in all patients before GH withdrawal. When compared with controls, before GH withdrawal, GHD adolescents had reduced high-density lipoprotein cholesterol levels and increased total/high-density lipoprotein cholesterol ratio, fibrinogen, low-density lipoprotein cholesterol, and glucose levels; non-GHD adolescents had increased glucose, insulin, and homeostasis model assessment score. IMT at the common carotid arteries was similar in GHD and controls (0.52 +/- 0.03 vs. 0.55 +/- 0.06 mm; P = 0.23) and was higher in non-GHD than in controls (0.62 +/- 0.03 vs. 0.54 +/- 0.06 mm; P = 0.01). In GHD adolescents, 6 months of GH treatment withdrawal and 6 months of GH treatment reinstitution modified IGF-I levels, lipid profile, and insulin resistance but not IMT or systolic and diastolic peak velocities at the common carotid arteries. In non-GHD subjects, 12 months of GH treatment withdrawal significantly decreased IGF-I levels, IMT (to 0.54 +/- 0.06 mm; P < 0.001 vs. baseline), systolic and diastolic peak velocities, and improved insulin resistance. In conclusion, the discontinuation of GH in confirmed GHD adolescents is not followed by significant alterations of the common carotid arteries, despite the profound negative alterations of the lipid profile. In adolescents who were not confirmed to have GHD, IMT was increased while on GH therapy and normalized when they were taken off of GH.     

Non-atherosclerotic coronary artery disease and sudden death in the young

Objective—To assess prevalence and type of non-atherosclerotic coronary artery disease in young people (≤35 years) who died suddenly.

Design—A necropsy study of 150 consecutive cases of sudden death (that is, within 6 h of the onset of symptoms).

Results—Death was attributed to coronary artery disease in 48 cases: in 16 (33%) of them the disease was non-atherosclerotic. Twelve subjects (eight males and four females, age range 2–35 years, mean 24·2) had congenital anomalies: a deep intramyocardial course in six, origin from the wrong sinus in three, and ostial obstructions in three. Sudden death was the first manifestation of disease in six cases. The other six had a history of palpitation or syncope or both. An electrocardiogram was available in five cases and showed ventricular arrhythmias in four; none had angina pectoris. Stress testing was available in two cases: neither showed any effort-dependent ST-T abnormalities. In six cases sudden death was related to physical exercise. Acquired non-atherosclerotic coronary artery disease was found in four cases: spontaneous coronary dissection in three previously symptom free patients and Kawasaki coronary arteritis in one child who had had acute myocardial infarction.

Conclusion—One third of the cases of fatal coronary artery disease were non-atherosclerotic with coronary artery anomalies being the most frequent form. Coronary artery anomalies should be suspected in young patients who have symptoms of ventricular arrhythmias without any overt signs and symptoms of ischaemia.

     

Growth hormone secretion in diabetic retinopathy

Summary The plasma HGH response to insulin-induced hypoglycemia (0.2 U/kg) and the 24-h plasma HGH pattern during a normal day have been studied in 14 non obese long-term insulin-dependent diabetics with proliferative retinopathy, mean age 39 ± 2 (ranging between 24 and 50 years). Plasma glucose and FFA were also determined. The results were compared with those of 18 normal subjects of similar age and weight. The mean plasma HGH response to insulin in retinopathic diabetics was slightly lower (with no significant differences) than in controls in whom hypoglycemia was induced with a smaller dose of insulin (0.1 U/kg). This pattern of plasma HGH could be related to the delayed plasma glucose fall observed in retinopathic diabetics in comparison to normal subjects, even if the HGH peak after insulin in both groups (18.61 ± 4.32 ng/ml in retinopathic diabetics, 27.43 ± 4.19 in controls) did not seem to be correlated to the degree of hypoglycemia, but rather to the age of the subjects. Plasma HGH pattern, studied with blood samples taken every three hrs during a normal day, did not reveal differences between the diabetics and controls. Plasma glucose, however, was higher in retinopathic diabetics than in controls in spite of the insulin treatment. These results show that in diabetic patients with retinopathy, increased HGH secretion does not occur in conditions of ordinary life or after insulin-induced hypoglycemia, although the HGH plasma levels observed in retinopathic diabetics could be considered too high in relation to the elevated blood glucose levels. Traduzione a cura degli AA.     

Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers

Background

Immunoglobulin light chains are classified as middle molecule uremic toxins able to interact with B lymphocyte membranes leading to the activation of transmembrane signaling. The ensuing impairment of neutrophil function can contribute to the chronic inflammation state of uremic patients, and the increased risk of bacterial infections or vascular calcifications. The aim of this crossover observational study was to assess the difference in free light chain removal by three different hemodialysis filters in patients not affected by multiple myeloma.

Methods

Free light chain removal was compared in the polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17 filter and the conventional polysulfone filter F7HPS. Twenty chronic hemodialysis patients were enrolled: mean age was 67.7?±?17.0 years, M/F?=?14/6, dialysis vintage (months) 25.5?±?32.0. The patients were randomized into two groups of treatment lasting 6 weeks each. The dialysis sessions checked were the midweek sessions and the blood was drawn at times 0, 120’ and 240’. Kappa (k) and lambda (λ) light chain levels, β2microglobulin (β2M), C reactive protein (CRP) and albumin were checked.

Results

K light chain levels were 345.0?±?100.0 mg/L, λ light chains were 121.4?±?27.0 mg/L. The values of k light chains at times 120’ and 240’ were significantly lower with PMMA and HFR17 than those obtained with F7. The reduction ratio per session (RRs) for k light chains was 44.1?±?4.3% with HFR17, 55.3?±?3.4% with PMMA, 25.7?±?8.3% with F7 (p?=?0.018). The RRs for λ light chains was 30.3?±?2.9% with HFR17, 37.8?±?17.3% with PMMA, 14.0?±?3.9% with F7 (p?=?0.032). As to β2M, RRs was 42.4?±?3.2% with HFR17 vs. 33.9?±?2.8% with PMMA vs. 6.3?±?1.9% with F7 (p?=?0.022). The three filters tested showed no differences in CRP or albumin levels.

Conclusion

In terms of light chain and β2M removal, the PMMA and on-line HFR filters are similar and both are significantly more effective than the F7 filter in chronic dialysis patients.

Trial registration

The present trial was registered retrospectively (NCT02950389, 31/10/2016).