Moderate acute rejection detected during annual catheterization in pediatric heart transplant recipients.

BACKGROUND: Acute rejection commonly occurs within the first year after heart transplantation, and then decreases in frequency with time. Recently, the long-term utility of endomyocardial biopsy during routine annual catheterization has been questioned. The purpose of this study was to retrospectively review the prevalence of biopsy-proven rejection during routine annual catheterization in our patient population, determine whether biopsies late after transplant are useful, and identify factors that correlate with late unsuspected rejection. METHODS: Biopsy results from the annual catheterization were evaluated from 1986 to August 2000. The prevalence of moderate rejection was evaluated and compared with the patient's immunosuppressive regimen; the prevalence of late rejection; and how late rejection correlated with recipient age, number of first-year rejections and presence of sub-therapeutic cyclosporine. RESULTS: A total of 1108 biopsies were performed in 269 children with a mean follow-up of 5 +/- 3 years (median 5 years, range 1 to 11 years). Three-drug immunosuppressive therapy, including steroids, was used in 93 patients. There was a persistent 8% to 10% prevalence of moderate rejection at up to 10 years post-transplantation. Moderate rejection was more likely in patients: (1). on 3-drug immunosuppressive therapy; (2). with a recipient age >1 year; and (3). with a relatively lower cyclosporine level. CONCLUSIONS: These data suggest that continued surveillance of pediatric transplant patients for acute rejection is indicated for long-term follow-up.     

The impact of the Safe Kids/Healthy Neighborhoods Injury Prevention Program in Harlem, 1988 through 1991.

OBJECTIVES. This study evaluated the effectiveness of a community coalition to prevent severe injuries to children in Central Harlem, New York, NY. It was hypothesized that injury incidence rates would decline during the intervention (1989 through 1991) relative to preintervention years (1983 through 1988); that the decline would be greatest for the targeted age group (5 through 16 years) and targeted injury causes (traffic accidents, assaults, firearms, outdoor falls); and that the decline would occur in the intervention community rather than a control community. METHODS. Surveillance of injuries that result in hospitalization and/or death among children in the two communities has been under way since 1983. Data from this surveillance were used to test whether the incidence of severe injury declined during the intervention; other temporal variations were controlled by Poisson regression. RESULTS. The incidence of injury among school-aged children in central Harlem declined during the intervention. The decline was specific to the targeted age group and targeted causes. A nonspecific decline also occurred in the control community. CONCLUSIONS. The declining incidence rate in Central Harlem is consistent with a favorable program effect, but additional investigation of possible secular trend or spillover effects is needed.     

Secondary surfactant deficiencies in extremely low birth weight premature infants.]

Primary deficiency of surfactant is responsible for the respiratory distress syndrome and concerns premature neonates born before 33 weeks of gestation. However, newborns may develop respiratory disorders related to a secondary deficiency or dysfunction of surfactant. We report the course of three extremely low birth weight premature infants who experienced clinical respiratory decompensation at two weeks and showed a marked improvement after exogenous natural surfactant administration.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Impaired colour discrimination in Huntington's disease

Colour discrimination and visual contrast perception were investigated in 18 patients with Huntington's disease (HD) and in 18 age- and sex-matched healthy volunteers using the Farnsworth-Munsell 100 Hue test (FM) and stationary contrast targets. The mean total error score (MTES) and the partial scores for the “red-green” and the “blue-yellow” axes in the FM of the patients with HD were significantly elevated as compared to controls (MTES in HD: 113.0 ± 90.8; MTES in controls: 19.2 ± 8.8). The spatial contrast sensitivity in HD patients was normal. The colour perception dysfunction indicates that the visual system is affected in HD. The visual disorder may be related to an imbalance of certain neurotransmitters in the visual system of HD patients. Possible anatomical sites of the dysfunction responsible for colour discrimination abnormalities could be the retinal cone system and/or impaired parvocellular central visual pathways in HD.     

Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation.

Twenty-one patients with symmetric nonproliferative retinopathy who underwent extracapsular cataract extraction and intraocular lens implantation were followed up postoperatively for an average (+/- standard deviation) of 18 +/- 7 months to determine the incidence of progression of diabetic retinopathy, the final visual acuity, and factors predictive of progression of retinopathy and final visual acuity. Progression of retinopathy, defined as the development of clinically significant macular edema, an increase in intraretinal hemorrhages or hard exudate, or the development of proliferative diabetic retinopathy, was assessed in both eyes of 19 patients; in two remaining patients, dense preoperative cataract in the fellow eye precluded comparison of retinopathy progression in the operated-on eye to progression in the fellow eye. Overall, retinopathy progressed in 14 of 19 operated-on eyes (74%). Cataract extraction was highly associated with asymmetric progression of nonproliferative retinopathy; it progressed only in the operated-on eye in seven of 19 patients (37%), but in no patients did progression occur in the fellow eye alone (P = .0078). Women had a significantly increased risk of progression of retinopathy in the operated-on eye compared to men (P = .005). Visual acuity improved in 19 of 21 operated-on eyes (86%); however, only 11 eyes (52%) achieved a visual acuity of 20/50 or better and only six eyes (14%) achieved a visual acuity of 20/25 or better. In only five eyes was the final visual acuity in the operated-on eye more than two lines better than the final visual acuity in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

Pyogenic infections of the central nervous system secondary to dental affections—a report of six cases

Pyogenic infections of the central nervous system of dental origin are quite uncommon in industrialized countries. We report six cases with intracerebral (n=4) and intraspinal (n=2) infections treated in our hospital. The microbial pathogen was successfully isolated in all patients. Fusobacterium nucleatum as well as Streptococcus species were found in three cases. Bacillus species were identified in two patients. Actinomyces was the etiologic agent in one case. All patients suffered from dental pathologies, so that after clinical and radiological exclusion of other sources an oral focus was presumed. Therapeutic management consisted of an operative procedure in order to obtain decompression, as well as evacuation of the pus on the one hand, followed by targeted antibiotics on the other. Clinical improvement was achieved in all patients, with one patient lost to follow-up. On magnetic resonance tomography, the inflammatory changes also disappeared in all cases. We recommend that oral infection with recurrent bacteraemia should always be considered in the pathogenesis of the so-called “cryptic” intracerebral and intraspinal infections.     

Radical forequarter amputation with hemithoracectomy and free extended forearm flap: Technical and physiologic considerations

Background: A radical forequarter amputation with partial chest wall resection (one to four ribs) has been reported for benign and malignant lesions involving the shoulder and chest wall region. Concerns about reconstruction and postoperative pulmonary function have previously limited more extensive chest wall resections. The current report describes the first case in which a complete unilateral anterior and posterior chest wall resection and pneumonectomy (hemithoracectomy) accompany a forequarter amputation. A novel reconstructive technique used the full circumference of the forearm tissue with an intact ulna as a free osseomyocutaneous flap. Methods: In this case, a 21-year-old patient presented with an extensive recurrent desmoid tumor that involved the shoulder, brachial plexus, subclavian vein, and chest wall from the lateral sternal border to the midportion of the scapula and down to the eighth rib. The operative technique involved removal of the entire right hemithorax from the midline sternum to the transverse process posteriorly, down to the ninth rib inferiorly. Due to the absence of a rigid hemithorax, the uninvolved ipsilateral lung was also removed. The forearm flap was prepared before final separation of the specimen and division of the subclavian vessels. Results: Postoperatively, the patient maintained excellent oxygenation without atelectasis or fever and was extubated on the 15th postoperative day. As expected after pneumonectomy, significant decreases from preoperative to immediate postoperative values were noted for the vital capacity (VC) (from 4.87 L to 1.29 L), forced 1-s expiratory volume (FEV1) (from 3.77 L to 1.02 L), and inspiratory capacity (IC) (3.33 1 to 0.99 1). Rehabilitation included a specially designed external prosthesis to provide cosmesis and prevent scoliosis. By the 15th postoperative week the patient had returned to normal social and physical activities, with a gradual improvement in all respiratory parameters: VC 1.52 L, FEV1 1.29 L, IC 1.04 L. There has been no evidence of tumor recurrence at 1 year. Conclusions: This report provides evidence that a complete hemithoracectomy, pneumonectomy, and forequarter amputation can be safely performed for selective tumors involving the shoulder region with extensive chest wall invasion. Reconstruction may be achieved with an extended forearm osseomyocutaneous free flap with an excellent functional outcome. Presented at the 46th Annual Cancer Symposium of The Society of Surgical Oncology, Los Angeles, California, March 18–21, 1993.