Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Sleep polygraphy in Angelman syndrome.

OBJECTIVE: Sleep disturbances are frequent in Angelman syndrome (AS); however, beside the few studies which have investigated sleep disorders in AS by means of questionnaires, to our knowledge, no systematic polysomnographic recordings have been carried out in AS patients. The present study represents the first attempt to study sleep patterns of AS by polysomnography, to evaluate the influences of sleep on the paroxysmal electroencephalogram (EEG) patterns of AS and to assess the eventual age-related changes of sleep architecture and of sleep EEG abnormalities in children and adolescents with AS. METHODS: Fifteen children with AS (7 males and 8 females, mean age 7.2 years, range 3-16 years), attending the Sleep Center of the Department of Child Neurology and Psychiatry of the University of Rome 'La Sapienza' and the Sleep Research Centre of the Oasi Institute (IRCCS) of Troina were included and subdivided into two subgroups by age: subgroup 1, aged 3-5 years, and subgroup 2, aged 9-17 years. Two control groups of age-matched normal subjects were also included: one aged less than 8 years and another aged more than 8 years; additionally, two other groups of age-matched children with epilepsy and mental retardation of different origin, one aged less and one aged more than 9 years were taken into consideration. The statistical comparison between the sleep parameters obtained from the patients and those from the other groups was carried out by means of the non-parametric Kruskal-Wallis ANOVA and the Mann-Whitney U test. RESULTS: The most frequent EEG abnormality found in AS patients appeared to be the 2-3 c/s poorly defined spike/waves complexes. This pattern was influenced by sleep stages; the duration of the runs showed an increasing length with sleep deepening from sleep stage 1 to slow-wave sleep (SWS). Moreover, the 2-3 c/s bursts activity present in sleep stage 2 showed a slowing to 1-2 c/s during SWS. Regarding sleep architecture, in subjects with AS aged <8 year there was a significant reduction in sleep efficiency as compared to normal controls, while the percentage and duration of REM sleep was significantly lower and the percentage of SWS was significantly higher. REM sleep time was reduced in AS subjects aged >8 years than in normal controls. The comparison between AS groups and mental retardation with epilepsy groups did not show significant differences. CONCLUSIONS: Similarly to other types of genetically determined mental retardation syndromes, also subjects with AS seems to show important abnormalities of their sleep polysomnographic patterns. SIGNIFICANCE: This is the first study which reports, in detail, these abnormalities and opens a new path for further insight into the knowledge of additional sleep-related disturbances which are reported in sleep questionnaires by the caregivers of AS subjects.     

Neuroendocrine and clinical effects of transdermal 17β-estradiol in postmenopausal women

The neuroendocrine and clinical effects of transdermal 17β-estradiol (rated at 50 μg/day; TTS 50) were studied in 40 postmenopausal women; ten additional postmenopausal women did not receive any drugs. The changes in LH and rectal temperature induced by the infusion of the opioid antagonist naloxone (10 mg i.v. bolus plus 10 mg/h for 4 h) were used to evaluate the central activity of endogenous opioid peptides. TTS 50 increased opioid activity, as evidenced by the restoration of the LH response (P < 0.01) and the enhancement of the hypothermic effect (P < 0.05) of naloxone. A greater reduction in hot flushes was observed in TTS 50-treated subjects than in untreated women, with the maximal effect of TTS 50 achieved after 3 months of therapy. TTS 50 did not modify the concentrations of circulating lipids, glucose or liver enzymes but reduced the biochemical parameters indicative of bone reabsorption. Bone density of the distal radius significantly increased during TTS 50 (P < 0.02), reaching its maximum value after 6 months of therapy. Thereafter bone density declined, but more slowly than in untreated women.

Our data suggest that TTS 50 has marked neuroendocrine effects, that it diminishes the incidence of hot flushes and reduces bone demineralization. By contrast, it has a very little, if any, metabolic impact on the liver or on glucose and lipid metabolism.     

Functional Outcome After Surgical Treatment of Esophageal Perforation

Background. The functional results after treatment of intrathoracic esophageal perforations have been poorly documented.

Methods. A retrospective review of 42 patients who underwent treatment of intrathoracic esophageal perforation associated with benign esophageal disease was performed.

Results. Of 42 patients treated for esophageal perforation, 25 underwent primary repair, 15 underwent esophagectomy and reconstruction, 1 underwent cervical esophagostomy and drainage followed by esophageal resection, and 1 had drainage alone followed by primary repair. Among the patients treated with primary repair, at least one additional operation was required in 13 patients. Of the 15 patients treated with esophagectomy and reconstruction, none required further operative treatment. Follow-up averaged 3.7 years, and of the 36 survivors available for follow-up, 18 (50%) required at least one esophageal dilation postoperatively, and 3 (8.3%) have required regular dilations. Subjectively, 19 of 36 patients (53%) indicate that their swallowing is better than before perforation, it was the same in 12 (33%), and worse in 4 (11%).

Conclusions. In conclusion, approximately one third of patients surviving primary repair of esophageal perforations have continued difficulty with swallowing, which often requires esophageal dilations or esophageal reconstructive procedures, or a combination of both. Optimal long-term results are achieved when primary repair is performed in patients with motor disorders or a “normal” esophagus. Esophagectomy is a better option in those patients with strictures or diffuse esophageal disease.     

Mono- and bi-allelic expression of insulin-like growth factor II gene in human muscle tumors

Insulin-like growth factor II (IGF-II) is a mitogen for manycell types and an important modulator of muscle growth and differentiation.IGF-II gene is prevalently expressed during prenatal developmentand its gene activity is regulated by genomic imprinting, inthat the allele inherited from the father is active and theallele inherited from the mother is inactive in most normaltissues. IGF-II expression is activated in several types ofhuman neoplasms and an alteration of IGF-II imprinting has beendescribed in Beckwith–Wiedemann syndrome and Wilms' tumour.Here we show that monoallelic expression of IGF-II gene is conservedin normal adult muscle tissue whereas two or more copies ofactive IGF-II alleles, arising by either relaxation of imprintingor duplication of the active allele, are found in 9 out of 11(82%) rhabdomyo-sarcomas retaining heterozygosity at 11p15,regardless of the histological subtype. Since IGF-II has beenindicated as an autocrine growth factor for rhabdomyosarcomacells, these findings strongly suggest that acquisition of adouble dosage of active IGF-II gene is an important step forthe initiation or progression of rhabdomyosarcoma tumorigenesis.Among different types of muscle tumors, relaxation of imprintingseems to arise prevalently in rhabdomyosarcomas, since we havedetected only one case of partial reactivation of the maternalIGF-II allele out of 7 lelomyosarcomas tested.     

Comparison of three computer scanning modes as an interface method for persons with cerebral palsy.

Occupational therapists are becoming increasingly involved with interface assessments. This involvement is improving the ability of persons with physical disabilities to interact with computers, augmentative communication aids, and other devices. The ability to use these devices facilitates participation in activities that would otherwise be much more difficult to pursue, such as communication, education, work, and recreation. The purpose of the present study was to systematically compare three basic modes of scanning--automatic, inverse, and step--with the use of a single-subject experimental design. Six subjects--3 with spastic and 3 with athetoid cerebral palsy--from a local school volunteered for the study. Results indicated that the 3 subjects with spastic cerebral palsy had the greatest difficulty using the automatic scanning mode. The 3 subjects with athetoid cerebral palsy had the most difficulty using the step scanning mode. The results of this study suggest that clients should attempt each scanning mode and that their performance with each mode be compared to ensure the most appropriate recommendations.     

A comparison between the Regnauld arthroplasty and osteotomies of the first ray for the treatment of hallux valgus

This article is a retrospective study comparing the efficacy of Regnauld arthroplasty to first ray osteotomies for the treatment of hallux valgus. One hundred consecutive cases of Regnauld arthroplasties were compared with 100 consecutive first ray osteotomies. One hundred fourty-one patients were available for follow-up, and based on clinical/radiographic examinations, 72 were treated with the osteotomy protocol (group A) and 69 with Regnauld arthroplasty (group B). Age at surgery, clinical symptoms, and preoperative radiologic findings were similar for the 2 groups; there was a preponderance of female patients (90%). The average follow-up was 49 months in group A and 51 months in group B. Clinical evaluation showed in the osteotomy group a more stable correction (79% v 49%), greater pain reduction (measured in a visual analog scale from 0 = pain free to 10 = deep intolerable pain), increased residual articular excursion of the first metatarsophalangeal joint (27 degrees of active dorsiflexion from neutral position v 8 degrees ), and less presence of central metatarsalgia (15% v 34%) (P <.05). The radiographic evaluation expressed more stable correction values in group A for the following parameters: joint preservation, sesamoid position, intermetatarsal angle (7 degrees v 12 degrees ), abduction angle of the hallux (14 degrees v 20 degrees ), and proximal articular set angle (8 degrees v 18 degrees ) (P <.05).     

Hand hygiene and glove use behavior in an Italian hospital.

In an Italian hospital, we observed that hand hygiene was performed in 638 (19.6%) of 3,253 opportunities, whereas gloves were worn in 538 (44.2%) 1,218 of opportunities. We observed an inverse correlation between the intensity of care and the rate of hand hygiene compliance (R2=0.057; P<.001), but no such association was observed for the rate of glove use compliance (R2=0.014; P=.078). Rates of compliance with hand hygiene and glove use recommendations follow different behavioral patterns.