Nutritional therapy in cirrhosis

Abstract   In recent years increasing interest has been given to nutritional therapy in a variety of chronic diseases, including cirrhosis. Protein/calorie malnutrition is a common feature of advanced liver disease, and considerably affects prognosis. Hence, the need for nutritional support to provide patients with the minimum protein requirements to balance increased catabolism. Although most patients tolerate normal protein supply, in subjects with impending encephalopathy a nutritional support with branched-chain amino acids (BCAA) was suggested on the basis of neuro-pharmacological studies. A large, randomized trial has recently provided evidence that BCAA may be superior to equicaloric and equinitrogenous supplements, improving survival and retarding hepatocellular failure. Administration schedules including a late evening supplementation may be particularly helpful. Biochemical studies are providing the rationale for the beneficial effects, showing that leucine may be an important regulator of amino acid/protein metabolism.     

Serum levels of tumour necrosis factor-α predict response to recombinant human erythropoietin in patients with myelodysplastic syndrome

Summary We measured pretreatment serum levels of tumour necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF-α and IL-1β levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1–2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-α (80.5 ± 64.8 vs 8.1 ± 4.2 ng/l, P < 0.001) and IL-1β (60.4 ± 49.9 vs 8.9 ± 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF-α than non-responders (21.6 ± 26.2 vs 106.3 ± 60.8 ng/l, P < 0.001), whereas IL-1β concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 ± 48.9 vs 73.4 ± 48.2 ng/l, P= 0.120). It is noteworthy that TNF-α levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-α or IL-1β values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-α levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.     

Genetic control of the immune response to a synthetic vaccine against Plasmodium falciparum

Two independent vaccination trials using a hybrid synthetic polypeptide containing epitopes from four proteins of Plasmodium falciparum were performed. In the first trial 63 and in the second 122 volunteers were vaccinated, using different immunization schedules. The analysis of the humoral response to the vaccine, measured by IgG antibody titres to the polypeptide showed a bimodal distribution in both cases suggesting genetic control of the immune response to this protein. There was a small group of low or non-responders and a large group of good responders. HLA phenotyping of the two groups disclosed an association of the low responders to HLA-DR4 antigens with chi-square P value of 0.00039 when compared with the good responders group. These findings provide evidence for the genetic control of the immune response to the synthetic vaccine by the association of this response with particular alleles of the HLA class II antigens; such findings may lead to an explanation of the mechanism involved in disease susceptibility and need to be used in the design of a totally effective vaccine.     

Power Spectral Analysis of Cardiovascular Variability in Patients at Risk for Sudden Cardiac Death

Heart Rate Variability. The time series of successive heart periods present important variations around its mean value, determining the phenomenon of heart rate variability (HRV), assessed with both time and frequency domain approaches. A low standard deviation of the heart period (a time domain index of HRV) is a powerful prognostic indicator of sudden coronary death in patients recovering from acute myocardial infarction. Spectral analysis of HRV usually demonstrates two major components: indicated as LF (low frequency, ～ 0.1 Hz) and HF (high frequency, ～ 0.25 Hz). They are defined by center frequency and associated power, which is expressed in msec² or normalized units. When assessed in normalized units, LF and HF provide quantitative indicators of neural control of the sinoatrial node. Numerous experimental and clinical studies have consistently indicated that the LF component is a marker of sympathetic modulation and HF a marker of vagal modulation; the LF/HF ratio is a synthetic index of sympathovagal balance. In the analysis of 24-hour Holter recordings of normal subjects, a circadian rhythmicity of spectral markers of sympathetic and vagal modulation is clearly present, with a sympathetic predominance during the day and a vagal predominance during the night. In patients recovering from an acute myocardial infarction, spectral analysis of HRV revealed an increased sympathetic and decreased vagal activity during early convalescence, and a return to their normal balance by 6 to 12 months. A clear increase of LF was also evident in patients studied within a few hours of the onset of symptoms related to an acute myocardial infarction, independent of its location. Similarly, LF increased during transient myocardial ischemia. An increase in markers of sympathetic activity has also been observed prior to episodes of malignant arrhythmias. Spectral analysis of HRV could help in the understanding of the role of abnormal neural mechanisms in sudden coronary death, thus contributing to its prevention.     

Diagnostic evaluation of a synthetic peptide derived from a novel antigen B subunit as related to other available peptides and native antigens used for serology of cystic hydatidosis

A synthetic peptide (GU4) derived from an antigen B (AgB) subunit was serologically compared with crude antigen (HCFA); immunopurified AgB and antigen 5 (Ag5), and two other synthetic peptides, for diagnosis of human cystic hydatidosis. GU4 was derived from the sequence of AgB/2, the novel AgB subunit described by us. The other two peptides: 65 (AgB mimotope) and 89–122 (Ag5 mimotope), were described by others. Antigens B and 5 showed higher diagnostic sensitivity than corresponding peptides. All sera reacting with peptides 89–122 and GU4 also reacted with 65. The latter provided three to four times higher sensitivity than the former two peptides, but 30% lower specificity. The diagnostic efficiency of AgB (82%) was higher than those of Ag5 (74%) and HCFA (71%). Interestingly, 89–122 only reacted with hydatid sera, some of which did not react with AgB. Considering positive those reacting with 89–122 or AgB, sensitivity increases from 77% (with AgB) to 82% (combined), while specificity is the same as with AgB (86%). Our results suggest that hydatid serology may be improved by: a) combining several defined antigens (including synthetic peptides), b) design of new E. granulosus-specific mimotopes, which react with the false negative sera (16/90; 18%).     

Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients

Duchenne Muscular Dystrophy (DMD) is the most common muscle disease in children. Historically, DMD results in loss of ambulation between ages 7 and 13 years and death in the teens or 20s. In order to determine whether survival has improved over the decades and whether the impact of nocturnal ventilation combined with a better management of cardiac involvement has been able to modify the pattern of survival, we reviewed the notes of 835 DMD patients followed at the Naples Centre of Cardiomyology and Medical Genetics from 1961 to 2006. Patients were divided, by decade of birth, into 3 groups: 1) DMD born between 1961 and 1970; 2) DMD born between 1971 and 1980; 3) DMD born between 1981 and 1990; each group was in turn subdivided into 15 two-year classes, from 14 to 40 years of age. Age and causes of death, type of cardiac treatment and use of a mechanical ventilator were carefully analyzed.The percentage of survivors in the different decades was statistically compared by chi-square test and Kaplan-Meier survival curves analyses. A significant decade on decade improvement in survival rate was observed at both the age of 20, where it passed from 23.3% of patients in group 1 to 54% of patients in group 2 and to 59,8% in patients in group 3 (p < 0.001) and at the age of 25 where the survival rate passed from 13.5% of patients in group 1 to 31.6% of patients in group 2 and to 49.2% in patients in group 3 (p < 0.001).The causes of death were both cardiac and respiratory, with a prevalence of the respiratory ones till 1980s. The overall mean age for cardiac deaths was 19.6 years (range 13.4-27.5), with an increasing age in the last 15 years. The overall mean age for respiratory deaths was 17.7 years (range 11.6-27.5) in patients without a ventilator support while increased to 27.9 years (range 23-38.6) in patients who could benefit of mechanical ventilation.This report documents that DMD should be now considered an adulthood disease as well, and as a consequence more public health interventions are needed to support these patients and their families as they pass from childhood into adult age.Key words: Duchenne, survival, cardiomyopathy     

The Implantable Cardioverter-Defibrillator: Clinical Results

To evaluate the effectiveness of the automatic implantable cardioverter-defibrillator (AICD), a 7-year experience, from 1983–1990, was reviewed. A total of 111 patients received an AICD device. Their ages ranged between 8 and 83 years. Mean age was 63.9 years. There were 91 men and 20 women. Eighty of the patients received the AICD following an out-of-hospital cardiac arrest, white 32 were suffering from intermittent symptomatic ventricular tachycardia. The underlying etiology in 97 patients (87%) was ischemic coronary artery disease, in 11 patients (10%) dilated cardiomyopathy, and in 3 patients (3%) idiopathic ventricular fibrillation. Mean ejection fraction was 33.2%. Implantation of the AICD was performed via a left thoracotomy in 39 patients, median sternotomy in 49 patients and subxiphoidsubcostal approach in 23 patients. In-hospital mortality occurred in one patient who suffered an acute myocardial infarction 4 hours postoperatively. Out-of-hospital mortality was observed in 19 patients. There were two arrhythmic deaths. Follow-up was available for 107 patients. Mean follow-up was 33.1 months. Sixty-six patients (62%) had AICD shocks. The initial appropriate shocks occurred during the first postimplantation year in 91% of the patients. In 53 of the survivors, initial AICD shocks took place within 4.4 ± 4.7 months from implantation. Thirteen of the 20 patients who died had received appropriate AICD shocks. In these patients, the time between implantation and first shock was 2.7 ± 3.6 months whereas the time between implantation and death was 11.3 ± 10.3 months (NS). We conclude that the AICD is effective in converting ventricular tachyarrhythmias and prolongs survival.     

Two False-negative Responses to the Ajmaline Test in the Wolff-Parkinson-White Syndrome

Anterograde block in the accessory pathway with a short effective refractory period was observed after intravenous (IV) injection of 1 mg/kg of ajmaline in two patients with the Wolff-Parkinson-White syndrome. The possibility of a false-negative response to this test is discussed. Ajmaline is proposed as an emergency drug in the Wolff-Parkinson-White syndrome in the setting of atrial fibrillation with a very high ventricular rate.