The combined use of extracorporeal life support and the Berlin Heart pulsatile pediatric ventricular assist device as a bridge to transplant in a toddler

There is a very limited published material about experience with long-term pediatric mechanical circulatory support as a bridge to heart transplant. We report on a 2-year-old, 12 kg boy admitted with 2-week history of low-grade fever, ear pain, pulmonary edema, and congestive heart failure. Trans-thoracic echocardiography confirmed severe myocardial dysfunction with a left ventricular ejection fraction of 0.20 and percentage shortening of 13. After 2 days of ventilatory and inotropic support, the patient continued to deteriorate and subsequently required femoro-femoral extracorporeal life support (ECLS). This was later complicated by a progressive coagulopathy and massive bleeding. On day 17, a pulsatile pediatric paracorporeal biventricular assist device (VAD) (Berlin Heart) was implanted. The patient's condition improved significantly with all coagulopathies corrected, and the patient was extubated 21 days later. After 109 days of bi-VAD support, the patient was successfully transplanted and discharged home 45 days post transplant. Our early experience with initial ECLS bridge to VAD and subsequently to transplant was encouraging. It allowed for additional time to select the ideal organ donor and optimize the recipient's comorbid condition and multiorgan failure. VAD provides an additional armamentarium of circulatory support in pediatric patients with severe heart failure.     

Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations

BACKGROUND: An elevated plasma homocysteine (Hcy) level has been prospectively associated with an increased risk of vascular and degenerative dementias. An Hcy elevation is prevalent in patients with Parkinson disease (PD) in part because levodopa metabolism produces Hcy. The clinical relevance of an elevated Hcy level in patients with PD is unknown. OBJECTIVE: To determine if hyperhomocysteinemia in patients with PD is associated with depression or with cognitive or physical impairments. DESIGN: Ninety-seven people with a mean (SD) PD duration of 3.6 (1.6) years completed the Beck Depression Inventory, a battery of 11 cognitive tests, and the motor and function components of the Unified Parkinson's Disease Rating Scale. Normalized scores for the affective, cognitive, and physical measures were compared between those with a normal Hcy level (n = 66) and those with hyperhomocysteinemia (n = 31) (Hcy level, >1.89 mg/L [>14 micro mol/L]), controlling for age, sex, disease duration, and treatment. RESULTS: Subjects with an elevated Hcy level were slightly older (68 vs 62 years), but had similar plasma concentrations of vitamin B(12) and folate. Hyperhomocysteinemic patients were more depressed (P =.02) and had worse cognition (P<.01), but the physical measure did not differ. CONCLUSIONS: Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients. Further research is warranted to see if hyperhomocysteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.     

Regulation of attention and response to therapy in dementia by butyrylcholinesterase

OBJECTIVES: To determine the response of patients with different butyrylcholinesterase genotypes to therapy, and the influence of butyrylcholinesterase on cognition. Acetylcholine plays a key role in attention and memory and reduced cortical acetylcholine is associated with the severity of dementia. Inhibitors of the enzyme acetylcholinesterase are an effective dementia treatment, though the role of the related enzyme butyrylcholinesterase is less well understood. METHODS: We examined the response of a cohort of dementia patients enrolled in a trial of a cholinesterase inhibitor who had been genotyped at the butyrylcholinesterase locus. Additionally a prospectively assessed cohort of dementia patients was genotyped and rate of cognitive decline examined, along with baseline cognitive performance in a group of elderly non-demented individuals. We identified that the presence of reduced-activity butyrylcholinesterase variants correlates with preserved attentional performance and reduced rate of cognitive decline. During cholinesterase inhibitor therapy, patients with normal butyrylcholinesterase show improved attention, though patients carrying reduced-activity enzyme do not, possibly due to being at ceiling performance. Butyrylcholinesterase did not however affect attentional performance in non-demented individuals with mild cognitive impairment. CONCLUSIONS: These findings indicate that the butyrylcholinesterase enzyme is a major regulator of attention especially in cholinergic deficiency states through its ability to hydrolyse acetylcholine. Pharmacologic manipulation of this enzyme may be a viable strategy in dementia treatment and, with butyrylcholinesterase genotyping, may provide pharmacogenomic treatment of dementia.     

The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.     

Prospective ultrasound diagnosis of Pallister-Killian syndrome in the second trimester of pregnancy: the importance of the fetal facial profile

The Pallister-Killian syndrome (PKS) represents a rare polymalformative complex characterized by a tissue-specific mosaic distribution of an additional isochromosome 12p and characterized by diaphragmatic hernia, rhizomelic limb shortening, facial anomalies and, rarely, acral hypoplasia. Since diaphragmatic hernia and acral hypoplasia can be also found in Fryns syndrome, the differential diagnosis between the two conditions depends on the demonstration of the 12p isochromosome by FISH. Prenatal diagnosis of PKS has been reported in cases submitted to karyotyping due to advanced maternal age or congenital anomalies detected on second trimester ultrasound. Among the ultrasound-detected malformations, little attention has been paid to facial anomalies. We describe a case in which PKS was prospectively suspected on the basis of the various anomalies detected at ultrasound, namely diaphragmatic hernia, rhizomelic limb shortening, and abnormal facial profile. The diagnosis was then confirmed by FISH on amniocytes and peripheral lymphocytes. In the present case, the disclosure of typical facial abnormalities significantly contributed to the differentiation between PKS and Fryns syndrome.     

Prenatal diagnosis of congenital heart disease in the Naples area during the years 1994-1999 -- the experience of a joint fetal-pediatric cardiology unit

OBJECTIVES: To analyse the spectrum and frequencies of observed malformations; to evaluate associated extracardiac and chromosomal anomalies and outcomes in each diagnostic category; to demonstrate the need for a multidisciplinary approach to the diagnosis of CHD in the fetus. METHODS: From January 1994 to December 1999, 450 cases of CHD were detected among 4052 pregnancies at risk of fetal CHD seen at our combined unit. Confirmation of the diagnosis was not available in 50 cases, leaving 400 cases for analysis. From our computerized database, the following variables were retrieved and analysed: indication, gestational age at diagnosis, associated extracardiac anomalies, karyotype, natural history, pregnancy and feto-neonatal outcome. RESULTS: CHDs most commonly detected were VSD (75 cases), AVSD (40 cases) and HLH (37 cases). The aneuploidy rate was 29.3% in the 355 cases submitted for karyotyping (25.9% in the whole series), with a prevalence of trisomy 21 and 18 (48 and 30 cases, respectively). The aneuploidy rate was highest for AVSD (80%), coarctation (49%), tetralogy of Fallot and VSD (45%). Associated extracardiac anomalies were present in 29.5% of the cases (118/400). As for pregnancy outcome, there were 150 (37.5%) terminations of pregnancy, 16 (4%) intrauterine fetal deaths and 85 (21.3%) neonatal deaths. The remaining 149 neonates are alive (37.3% survival rate). The termination rate for pregnancies in which CHD was detected at a gestational age <25 weeks was 65.2%. Evolutive changes determined progressive prognostic deterioration in 21 cases (5%), consisting of semilunar valve obstructions and development of ventricular hypoplasia. CONCLUSIONS: The high association rate with extracardiac and chromosomal anomalies (29.3% and 25.9%) and the possible progressive prognostic deterioration require a multidisciplinary team for correct management and follow-up. Survival of fetuses with certain CHD is severely reduced, in comparison with postnatal figures, for the common association with aneuploidies.     

Hypotensive Response Magnitude and Duration in Hypertensives: Continuous and Interval Exercise

Background

Although exercise training is known to promote post-exercise hypotension, there is currently no consistent argument about the effects of manipulating its various components (intensity, duration, rest periods, types of exercise, training methods) on the magnitude and duration of hypotensive response.

Objective

To compare the effect of continuous and interval exercises on hypotensive response magnitude and duration in hypertensive patients by using ambulatory blood pressure monitoring (ABPM).

Methods

The sample consisted of 20 elderly hypertensives. Each participant underwent three ABPM sessions: one control ABPM, without exercise; one ABPM after continuous exercise; and one ABPM after interval exercise. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and double product (DP) were monitored to check post-exercise hypotension and for comparison between each ABPM.

Results

ABPM after continuous exercise and after interval exercise showed post-exercise hypotension and a significant reduction (p < 0.05) in SBP, DBP, MAP and DP for 20 hours as compared with control ABPM. Comparing ABPM after continuous and ABPM after interval exercise, a significant reduction (p < 0.05) in SBP, DBP, MAP and DP was observed in the latter.

Conclusion

Continuous and interval exercise trainings promote post-exercise hypotension with reduction in SBP, DBP, MAP and DP in the 20 hours following exercise. Interval exercise training causes greater post-exercise hypotension and lower cardiovascular overload as compared with continuous exercise.