Cardiac status after childhood growth hormone treatment of Turner syndrome

CONTEXT: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment. METHODS: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived. RESULTS: Thirty-one patients [mean (sd) age 20 (2) yr, body surface area 1.75 (0.15) m(2), 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13) m(2)] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m(2) vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m(2) vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m(2) vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher mean heart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable. CONCLUSION: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe.     

Double outlet right ventricle assessed with Magnetic Resonance Imaging

In this article the value of magnetic resonance (MR) imaging for the evaluation of double outlet right ventricle (DORV) is reviewed from the literature and illustrated with several cases. MR imaging can be used for the determination of cardiac anatomy at initial diagnosis and may provide functional information during the follow-up of patients after surgical correction.     

Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis

Adjuvant arthritis (AA) can be induced in Lewis rats by immunization with mycobacterial antigens. Passive transfer of a T cell clone recognizing the 180–188 amino acid sequence in mycobacterial heat shock protein 60 (hsp60) was found to induce AA. In the present study, we investigated whether tolerance was obtained for this AA-associated T cell epitope after intranasal or s.c. administration of a peptide containing this epitope. Two 15-mer peptides containing the mycobacterial hsp60 sequences 176–190 and 211–225 were used; 176–190 contained the T cell epitope 180–188, which was recognized by the arthritogenic T cell clone A2b and was the immunodominant hsp60 T cell epitope after induction of AA, and 211–225 contained a T cell epitope that was recognized both after induction of arthritis with whole Mycobacterium tuberculosis and after immunization with mycobacterial hsp60. In rats treated intranasally or subcutaneously with 176–190 and immunized with mycobacterial hsp60, proliferative responses to 176–190 were reduced. Proliferative responses to 211–225 and to whole mycobacterial hsp60 were not affected. AA was inhibited intranasally in the 176–190-treated rats but not in the 211–225-treated rats. Moreover, intranasal 176–190 led to similar arthritis-protective effects in a nonmicrobially induced experimental arthritis (avridine-induced arthritis). Therefore, tolerance for a disease-triggering, microbial cartilage-mimicking epitope may cause resistance to arthritis irrespective of the actual trigger leading to development of the disease.     

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial

BACKGROUND: To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial by an open-label follow-up study lasting 4 years. METHODS: The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double-blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open-label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5-25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. RESULTS: Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P = 0.01) and 15% (P = 0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. CONCLUSIONS: Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension.     

R56865, a Na- and Ca-Overload Inhibitor, Reduces Myocardial Ischemia-Reperfusion Injury in Blood-Perfused Rabbit Hearts

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites or of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 ± 2.8 mmHg in group II and 31.3 ± 8.1 mmHg in group III vs 45.0 ± 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 ± 5.4%, 98.9 ± 6.1%, 85.3 ± 4.8% of baseline values, respectively, in group II, to 64.5 ± 3.0% (P > 0.05), 76.8 ± 3.0%, 70.2 ± 4.0% in group III, vs 52.0 ± 6.5%, 58.9 ± 6.9% and 53.6 ± 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 ± 2.2 ml/min and 19.8 ± 1.8 ml/min in groups II and III vs 14.8 ± 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca²⁺-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.     

Novel risk factors for peripheral arterial disease in young women

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.     

Endothelial progenitor cell capture by stents coated with antibody against CD34: the HEALING-FIM (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth-First In Man) Registry

OBJECTIVES: This study was designed to evaluate whether rapid endothelialization of stainless steel stents with a functional endothelium prevents stent thrombosis and reduces the restenotic process. BACKGROUND: A "pro-healing" approach for prevention of post-stenting restenosis is theoretically favored over the use of cytotoxic or cytostatic local pharmacologic therapies. It is believed that the central role of the vascular endothelium is to maintain quiescence of the underlying media and adventitia. METHODS: Sixteen patients with de novo coronary artery disease were successfully treated with implantation of endothelial progenitor cell (EPC) capture stents. RESULTS: Complete procedural and angiographic success was achieved in all 16 patients. The nine-month composite major adverse cardiac and cerebrovascular events (MACCE) rate was 6.3% as a result of a symptom-driven target vessel revascularization in a single patient. There were no other MACCE despite only one month of clopidogrel treatment. At six-month follow-up, mean angiographic late luminal loss was 0.63 +/- 0.52 mm, and percent stent volume obstruction by intravascular ultrasound analysis was 27.2 +/- 20.9%. CONCLUSIONS: This first human clinical investigation of this technology demonstrates that the EPC capture coronary stent is safe and feasible for the treatment of de novo coronary artery disease. Further developments in this technology are warranted to evaluate the efficacy of this device for the treatment of coronary artery disease.     

Effectiveness of Pulmonary Rehabilitation in Patients With Chronic Obstructive Pulmonary Disease With Different Degrees of Static Lung Hyperinflation

Objective

To evaluate the effect of pulmonary rehabilitation (PR) on exercise performance and quality of life in patients with chronic obstructive pulmonary disease (COPD) with different degrees of static lung hyperinflation (LH).

Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide,observational cohort study

Purpose

Chlorhexidine oral care is widely used in critically and non-critically ill hospitalized patients to maintain oral health. We investigated the effect of chlorhexidine oral care on mortality in a general hospitalized population.

Methods

In this single-center, retrospective, hospital-wide, observational cohort study we included adult hospitalized patients (2012–2014). Mortality associated with chlorhexidine oral care was assessed by logistic regression analysis. A threshold cumulative dose of 300 mg served as a dichotomic proxy for chlorhexidine exposure. We adjusted for demographics, diagnostic category, and risk of mortality expressed in four categories (minor, moderate, major, and extreme).

Results

The study cohort included 82,274 patients of which 11,133 (14%) received chlorhexidine oral care. Low-level exposure to chlorhexidine oral care (≤?300 mg) was associated with increased risk of death [odds ratio (OR) 2.61; 95% confidence interval (CI) 2.32–2.92]. This association was stronger among patients with a lower risk of death: OR 5.50 (95% CI 4.51–6.71) with minor/moderate risk, OR 2.33 (95% CI 1.96–2.78) with a major risk, and a not significant OR 1.13 (95% CI 0.90–1.41) with an extreme risk of mortality. Similar observations were made for high-level exposure (>?300 mg). No harmful effect was observed in ventilated and non-ventilated ICU patients. Increased risk of death was observed in patients who did not receive mechanical ventilation and were not admitted to ICUs. The adjusted number of patients needed to be exposed to result in one additional fatality case was 47.1 (95% CI 45.2–49.1).

Conclusions

These data argue against the indiscriminate widespread use of chlorhexidine oral care in hospitalized patients, in the absence of proven benefit in specific populations.