Cutaneous and Disseminated Blastomycosis: A Pediatric Case Series

Abstract: Blastomycosis is a rare fungal infection that most often initially infects the lungs and can progress to disseminated involvement of the skin, bones, and central nervous system (CNS). Pediatric blastomycosis constitutes a small portion of total cases, but delay in diagnosis may result in significant morbidity. Seventeen pediatric cases of blastomycosis were identified at Children’s Hospital of Wisconsin from 1999 to 2009 through retrospective chart review; 53% had evidence of dissemination (bone, skin, or CNS) confirmed by culture. Six cases presented with cutaneous lesions, and five of these were found to have other systemic involvement. These five nonimmunosuppressed cases of primary pulmonary disease with cutaneous involvement plus dissemination to bone or the CNS are reported in detail. The diagnosis of blastomycosis in children is often delayed, and dissemination by the time of diagnosis may be more common than in adults. Cutaneous dissemination may occur in immunocompetent children, may indicate underlying systemic involvement, and can be more readily identified than symptoms of bony or neurologic involvement. These reported cases indicate the importance of dermatologists recognizing and investigating all potentially involved organ systems when a patient presents with characteristic skin lesions with or without a history of respiratory illness.     

The pentose phosphate pathway and pyruvate carboxylation after neonatal hypoxic-ischemic brain injury

The neonatal brain is vulnerable to oxidative stress, and the pentose phosphate pathway (PPP) may be of particular importance to limit the injury. Furthermore, in the neonatal brain, neurons depend on de novo synthesis of neurotransmitters via pyruvate carboxylase (PC) in astrocytes to increase neurotransmitter pools. In the adult brain, PPP activity increases in response to various injuries while pyruvate carboxylation is reduced after ischemia. However, little is known about the response of these pathways after neonatal hypoxia-ischemia (HI). To this end, 7-day-old rats were subjected to unilateral carotid artery ligation followed by hypoxia. Animals were injected with [1,2-¹³C]glucose during the recovery phase and extracts of cerebral hemispheres ipsi- and contralateral to the operation were analyzed using ¹H- and ¹³C-NMR (nuclear magnetic resonance) spectroscopy and high-performance liquid chromatography (HPLC). After HI, glucose levels were increased and there was evidence of mitochondrial hypometabolism in both hemispheres. Moreover, metabolism via PPP was reduced bilaterally. Ipsilateral glucose metabolism via PC was reduced, but PC activity was relatively preserved compared with glucose metabolism via pyruvate dehydrogenase. The observed reduction in PPP activity after HI may contribute to the increased susceptibility of the neonatal brain to oxidative stress.     

Effects of a 3‐month supplementation with a novel soluble highly viscous polysaccharide on anthropometry and blood lipids in nondieting overweight or obese adults

Background: High viscosity fibre is known to exert many beneficial effects on appetite and metabolism. It could potentially help in weight management, in dieting or nondieting individuals. The present study investigated the effects of the daily intake of a novel high viscosity polysaccharide (HVP) over 3 months in nondieting obese or overweight men and women. Methods: The study comprised a double‐blind, randomised controlled clinical trial. Participants ingested 5–15 g per day of either HVP (n = 29, experimental group) or inulin (n = 30, control group) for 15 weeks. Changes in anthropometry (weight, waist and hip circumferences), blood lipids and glucose tolerance were studied from the beginning to the end of administration. Compliance and tolerance were examined. Results: Differences appeared between HVP and inulin supplementation in female participants only. Mean (SD) decreases in body weight [1.6 (3.2) kg; approximately 2% of initial weight] and hip circumference [2.8 (3.6 ) cm] occurred in women of the HVP group but not in controls (Time × Group interactions, P ≤ 0.002). Total, high‐density lipoprotein and low‐density lipoprotein‐cholesterol were lower at the end of supplementation in the women of the HVP group compared to controls (P ≤ 0.021). No effect appeared in waist circumference and triacylglycerol. No difference was noted in the number or severity of the adverse effects reported in both groups. Adverse effects were mild and agreed with commonly reported reactions to intake of dietary fibre. Conclusions: Beneficial although modest effects appeared after several weeks of daily HVP intake in nondieting obese or overweight women. The effects of HVP should be investigated in the context of a weight loss programme.     

Metabolic panniculitis: alpha‐1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Panniculitis can be the initial presentation of both alpha‐1 antitrypsin deficiency and pancreatic disease. They can both present with abscess‐like draining nodules, but may present like other forms of panniculitis with erythematous nodules. It is important to consider these in the differential diagnosis of patients presenting with panniculitis. Alpha‐1 antitrypsin deficiency is a relatively common disorder mainly affecting the lungs and liver. It frequently goes undiagnosed, yet critical interventions can be made to minimize disease progression. Panniculitis associated with alpha‐1 antitrypsin deficiency can be difficult to treat. Pancreatic panniculitis occurs in less than 3% of patients with underlying pancreatic disease and is often associated with arthritis. Diagnosis and treatment of the underlying pancreatic disease is imperative.     

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.     

Acute non-Q wave cocaine-related myocardial infarction

Since our initial report in 1984 of six patients with AMI temporally related to cocaine use, we have observed 19 additional patients in whom ischemic chest pain syndromes occurred shortly after intranasal or IV use of cocaine or after smoking the drug. Seventeen patients (89 percent) developed non-Q wave infarction and two had Q-wave infarction. One patient manifested angina with striking ST-segment elevation. None of the patients had diabetes or hypertension, and all but one were cigarette smokers. The serum cholesterol level was 162 +/- 7 mg/dl. Four of the five patients who consented to coronary angiographic studies displayed normal coronary arteries, and one showed proximal stenosis of the right coronary artery. The cold pressor test was performed in seven patients; none had angina or ECG changes induced by cold stimulation. We conclude that T-wave infarction is a common form of an acute cardiac event related to cocaine abuse, and its pathogenesis may involve that of the cocaine-induced coronary vasospasm.     

Insulin resistance and the endothelium

There is increasing evidence of a parallel progression between insulin resistance and endothelial dysfunction, suggesting a close association between insulin action and the endothelium. Numerous studies have demonstrated that endothelial dysfunction occurs early in the insulin-resistant state and is predictive of future cardiovascular events. Similarly, insulin resistance has been associated with the metabolic syndrome, which also increases the risk of adverse cardiovascular outcomes. Approaches that improve endothelial dysfunction, such as treatment with statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or peroxisome proliferator-activated receptor gamma ligands, have been shown to prevent both diabetes and cardiovascular disease. This article reviews the relation between endothelial dysfunction and cardiovascular disease, assesses the endothelium in the spectrum of insulin resistance, and examines the effect of the thiazolidinediones on endothelial function.     

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.