Case report: Pneumatosis in a neonate with thrombocytopenia absent radius syndrome.

BACKGROUND: Thrombocytopenia absent radius (TAR) syndrome is a rare disease with an estimated prevalence of one in 200,000 live births. TAR is associated with cardiac and renal anomalies as well as gastrointestinal problems such as cow's milk protein allergy (CMPA). Typically neonates with CMPA present with mild intolerance, with few reports in the literature of more severe intolerance resulting in pneumatosis. We present a case of a male infant with TAR syndrome who developed gastric and colonic pneumatosis intestinalis. CASE DESCRIPTION: An eight-day-old male infant born at 36 weeks gestation with a diagnosis of TAR, presented with bright red blood in his stool. At this time he was on full formula feeds. Given continued bright red blood within his stool, an abdominal radiograph was obtained which was consistent with colonic and gastric pneumatosis. A complete blood count (CBC) was notable for worsening thrombocytopenia, anemia and eosinophilia. Once enteral feeds were held there was rapid resolution of the radiographic findings and resolution of his bloody stool. He was ultimately diagnosed with a CMPA. CONCLUSION: Though there are reports of CMPA in patients with TAR, the severity of this patient's presentation with both colonic and gastric pneumatosis is unique. Without the knowledge of the association of CMPA with TAR, this case could have been misdiagnosed and led to reintroduction of cow's milk containing formula, resulting in further complications. This case highlights the importance of a timely diagnosis and severity of CMPA in this population.

PPARalpha deficiency reduces insulin resistance and atherosclerosis in apoE-null mice.

PPARalpha is a ligand-dependent transcription factor expressed at high levels in the liver. Its activation by the drug gemfibrozil reduces clinical events in humans with established atherosclerosis, but the underlying mechanisms are incompletely defined. To clarify the role of PPARalpha in vascular disease, we crossed PPARalpha-null mice with apoE-null mice to determine if the genetic absence of PPARalpha affects vascular disease in a robust atherosclerosis model. On a high-fat diet, concentrations of atherogenic lipoproteins were higher in PPARalpha(-/-)apoE(-/-) than in PPARalpha(+/+)apoE(-/-) mice, due to increased VLDL production. However, en face atherosclerotic lesion areas at the aortic arch, thoracic aorta, and abdominal aorta were less in PPARalpha-null animals of both sexes after 6 and 10 weeks of high-fat feeding. Despite gaining as much or more weight than their PPARalpha(+/+)apoE(-/-) littermates, PPARalpha(-/-)apoE(-/-) mice had lower fasting levels of glucose and insulin. PPARalpha-null animals had greater suppression of endogenous glucose production in hyperinsulinemic clamp experiments, reflecting less insulin resistance in the absence of PPARalpha. PPARalpha(-/-)apoE(-/-) mice also had lower blood pressures than their PPARalpha(+/+)apoE(-/-) littermates after high-fat feeding. These results suggest that PPARalpha may participate in the pathogenesis of diet-induced insulin resistance and atherosclerosis.

Mitochondrial transcription factor A is increased but expression of ATP synthase beta subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in hearts of copper-deficient rats.

The mechanism(s) by which impaired mitochondrial respiratory function and the accumulation of lipid droplets and mitochondria in hearts of copper-deficient rats occur remains unclear. It is not known whether specific components of the regulatory pathway involved in mitochondrial biogenesis, such as mitochondrial transcription factor A (mtTFA) and nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2), are activated in copper deficiency. Little is known about gene expression of enzymes involved in fatty acid oxidation (FAO) in hearts of copper-deficient rats. Male weanling rats were fed copper-adequate (CuA), copper-deficient (CuD) or pair-fed (CuP) diets for 5 wk. Mitochondria and lipid droplet volume densities from electron micrographs were greater and there was an elevation in the mtTFA protein level in hearts of copper-deficient rats. DNA binding activities of NRF-1 and NRF-2 did not differ among the groups. Northern blot analysis of cardiac tissue revealed that transcripts of F(1)F(0)-ATP synthase subunit c were greater, but mRNA levels of ATP synthase beta subunit and the FAO enzyme, medium-chain acyl-CoA dehydrogenase (MCAD), were lower in hearts of copper-deficient rats. Long-chain acyl-CoA dehydrogenase (LCAD) mRNA levels did not differ among treatment groups. These results suggest that certain components of the mitochondrial biogenesis program are activated in hearts of copper-deficient rats. F(1)F(0)-ATP synthase beta subunit and MCAD transcript levels remain low, which may contribute to impaired mitochondrial respiratory function, decreased fatty acid utilization and lipid droplet accumulation in hearts of copper-deficient rats.

The role of proliferating cell nuclear antigen (PCNA) in differentiating idiopathic orbital inflammatory disease and lymphoid proliferations.

The purpose of the present study was to determine whether proliferating cell nuclear antigen (PCNA), an immunohistochemical marker for a nuclear protein abundant in actively proliferating (dividing) cells, is useful as an aid in differentiating idiopathic orbital inflammatory syndrome (IOIS) from lymphoproliferative lesions (LLs). Records of all patients with IOIS and LLs were studied retrospectively. Tissue biopsy specimens from four patients with IOIS and nine patients with LLs were examined. The diagnosis in each case was based on presenting signs and symptoms, orbital computed tomography (CT) and/or magnetic resonance (MR) scans, histopathologic criteria, and follow-up data consistent with the entity. These findings were correlated with the percentage of B- and T-cells in the lesions as well as with the number of cells that demonstrated staining for PCNA in formalin-fixed tissue. PCNA activity was markedly increased in the higher grade (HG) lymphoma group as compared to that in the low grade (LG) lymphoma and idiopathic inflammatory group. Lymphoma cases showed a significantly increased B-/T-cell ratio compared to IOIS lesions. PCNA activity in conjunction with the ratio of B-/T-cells may be a helpful immunohistologic adjunct for differentiating purely inflammatory lesions of the orbit from lymphoid tumors. Further studies are necessary to compare PCNA activity in fresh frozen tissue with that in formalin-fixed tissue.

Treatment selections of 239 patients with blepharospasm and Meige syndrome over 11 years.

BACKGROUND: A retrospective review of 239 patients with benign essential blepharospasm and Meige syndrome was performed in order to determine patients' long term treatment preferences. METHODS: Of 239 patients evaluated, 228 received local injections of botulinum toxin, type A, into the eyelid and facial musculature over 11 years. RESULTS: Of 228 patients, 202 (72.1%) were still treated with botulinum toxin, type A. Eighteen patients (6.9%) no longer received botulinum toxin injections and sought no other treatment. Five patients (2.2%) had apparent remission of their disease after injection. Three patients (1.3%) ultimately obtained relief from orbicularis muscle extirpative surgery and required no additional treatment. Two of the 11 patients (4.6%) who chose not to receive botulinum toxin injections were successfully treated with other modalities: psychotherapy (one patient) and oral haloperidol (one patient). CONCLUSION: While botulinum toxin is the most highly effective treatment for benign essential blepharospasm and Meige syndrome over a long period of time, adjunctive oral drug therapy, including minor tranquillisers as well as eyelid surgery, may augment its effectiveness.

Treatment choices of 119 patients with hemifacial spasm over 11 years.

A retrospective study of patients with hemifacial spasm (HFS) was performed in order to determine long-term treatment choices: local botulinum toxin, type A, injections, oral pharmacologic agents, and surgery (neurosurgical decompression of the seventh nerve at the brainstem level and upper eyelid blepharoplasty). Of 119 patients with diagnosed hemifacial spasm in the Oculoplastics Division of the Department of UMD-New Jersey Medical School, Newark, NJ from September, 1983, to June 1, 1994, 108 were initially treated with 735 botulinum toxin injections. Forty-seven of the 108 patients (43.5%) initially treated at our institution received 459 injections for a median treatment period of 59 months per patient. Eight patients (7.4%) continued treated elsewhere and four other patients were injected at our institution until their death from other causes. Twenty-two patients (20.4%) were lost to followup after receiving 117 injections. Five patients (4.6%) had spontaneous resolution of their condition after botulinum toxin therapy and nine patients (8.3%) chose not to receive any additional injections or other treatment. Thirteen patients (12.0%) did not respond adequately to botulinum injections and 10 such patients obtained relief from treatments other than botulinum toxin: oral pharmacologic agents (two patients), neurosurgical decompression of the seventh nerve (two patients), and upper eyelid blepharoplasty (one patient). In addition to botulinum injections, 15 patients required adjunctive minor tranquilizers and/or antiseizure medications. Botulinum A toxin is an excellent long-term treatment of hemifacial spasm. This condition may occasionally spontaneously resolve after botulinum therapy.

The human medium chain Acyl-CoA dehydrogenase gene promoter consists of a complex arrangement of nuclear receptor response elements and Sp1 binding sites.

Expression of the gene encoding the mitochondrial fatty acid. beta-oxidation enzyme, medium-chain acyl-CoA dehydrogenase (MCAD), is regulated among tissues during development and in response to alterations in substrate availability. To identify and characterize cis-acting MCAD gene promoter regulatory elements and corresponding transcription factors, DNA-protein binding studies and mammalian cell transfection analyses were performed with hjman MCAD gene promoter fragments. DNA:protein binding studies with nuclear protein extracts prepared from hepatoma G2 cells, 3T3 fibroblasts, or Y-1 adrenal tumor cells identified three sequences (nuclear receptor response element 1 or NRRE-1, NRRE-2, and NRRE-3) that bind orphan members of the steroid/thyroid nuclear receptor superfamily including chicken ovalbumin upstream promoter transcription factor and steroidogenic factor 1. Sp1 binding sites (A-C) were identified in close proximity to each of the NRREs. NRRE-3 conferred cell line-specific transcriptional repression by interacting with chicken ovalbumin upstream promoter transcription factor or activation via steroidogenic factor 1. In contrast, the Sp1 binding site A behaved as a transcriptional activator in all cell lines examined. We propose that multiple nuclear receptor transcription factors interact with MCAD gene promoter elements to differentially regulate transcription among a variety of cell types.