Acute suppurative thyroiditis in children

BACKGROUND: Acute suppurative thyroiditis in children is rare and is often related to a pyriform sinus fistula or thyroglossal duct remnant, especially when it is recurrent. METHODS: From January, 1985, through December, 2000, 15 children with acute suppurative thyroiditis were treated. Their clinical, laboratory and radiologic findings were reviewed and analyzed. RESULTS: There were 8 girls and 7 boys, with a mean age at diagnosis of 6.1+/-2.9 years (range, 1.5 to 9.8). A thyroid mass was present on the left in 13 and on the right in 2 (P < 0.05). Fever, neck pain and swelling were the most common symptoms and signs. Seven patients (46.7%) had recurrent disease. Needle aspiration for Gram stain and bacterial cultures were done, and pathogenic organisms were identified on culture in 8 patients but were found only on Gram stain in 2 patients. In one-half of the patients with positive cultures, mixed pathogens were found. The most common organisms isolated were streptococcal species (50%). Barium esophagography was performed in all patients, and 5 (33.3%) had a pyriform sinus fistula on the left. Only 1 of the recurrent patients had a fistula. Thyroid scans were performed in 13 patients, of whom 12 (92.3%) had decreased radioactive uptake. Thyroid function tests were normal in all 15. CONCLUSIONS: Acute suppurative thyroiditis is usually caused by oropharyngeal flora, resulting in mixed pathogens on culture. Broad spectrum antibiotics should be given once cultures have been obtained. Imaging studies might be helpful in the diagnosis of acute suppurative thyroiditis.     

Resilient RTN fast spiking in Kv3.1 null mice suggests redundancy in the action potential repolarization mechanism

Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.     

Glial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung's disease

Hirschsprung's disease (HSCR), a congenital disease, is characterized by the absence of ganglion cells in the ganglion plexuses of the caudal most gut. In the aganglionic colon, the plexus remnants are replaced by aggregates of glial cells and hypertrophied nerve fibers. Signaling of glial cell line-derived neurotrophic factor (GDNF)-GFRAs-receptor tyrosine kinase (RET) is crucial for the development and maintenance of ganglion cells. Mutations of genes such as GDNF and RET lead to the perturbation of this signaling pathway, which causes HSCR. To understand the role of GFRAs in ganglion cells and the pathogenesis of HSCR, we intended to determine the specific cell lineages in the enteric nervous system that normally express GFRAs but are affected in HSCR. We studied colon biopsy specimens from 13 patients with HSCR (aged 1 day to 38 months) and 6 age-matched patients without HSCR as normal controls. RT-PCR, in situ hybridization, and immunohistochemistry were performed to examine the expression and cellular distributions of GFRAs in resected bowel segments of normal infants and those with HSCR. In normal infants and normoganglionic colon of patients with HSCR, the expression of GFRA1 was restricted to the glial cells and neurones of the ganglion plexuses. GFRAs expression was found to be markedly reduced in the aganglionic colons of 3 infants with HSCR but was unaffected in the aganglionic colons of 10 other infants with HSCR. Residual GFRA expression was restricted to enteric glial cells in the plexus remnants of the aganglionic colons. Hypertrophied nerve fibers were not found to express GFRA1. We provide the first evidence that abnormal expression of GFRAs in the enteric nervous system may be involved in the pathogenesis of HSCR in a subpopulation of patients.     

Severe acute respiratory syndrome: radiographic evaluation and clinical outcome measures

PURPOSE: To evaluate the relationship among chest radiographs, oxygen supplementation requirement, and treatment response in severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Forty patients (20 women, 20 men; mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with SARS were evaluated. Daily chest radiographs were graded according to percentage of lung involvement during 20.15 days +/- 5.56 (median, 20 days; range, 14-38 days). Times between symptoms and treatment and time to reach maximal radiographic score from admission and treatment day were determined. Daily oxygen saturation (Sao2) and oxygen supplementation including mechanically assisted ventilation were recorded. Treatment response was defined as good, fair, and poor. Patterns of radiographic opacity at admission and at maximal radiographic score were noted. Differences in radiographic and clinical parameters with respect to oxygen supplementation and treatment response were respectively evaluated with Mann-Whitney and Kruskal-Wallis tests. RESULTS: Larger maximal radiographic scores, lower Sao2 at maximal radiographic change, longer time from treatment to maximal radiographic score (P <.01), and diffuse consolidation at maximal radiographic score were associated with oxygen supplementation. Parameters that influenced treatment response were time from symptom onset to treatment day (P =.003), time from admission to treatment day (P <.001), time to maximal radiographic score from treatment day (P =.001), maximal radiographic score (P =.009), Sao2 at maximal radiographic score (P =.13), and treatment radiographic score (P =.03). Fair responders had shorter time between admission and treatment than did either good (P <.001) or poor responders (P =.002) and shorter time between symptoms and treatment (P <.001) and lower treatment radiographic score (P =.012) than did good responders. Good (82%), poor (36%), and fair (33%) responders developed maximal chest radiographic scores within 4 days of treatment (P =.008). Radiographic patterns at both admission and maximal radiographic score did not influence treatment response. CONCLUSION: There are significant relationships among radiographic parameters, oxygen supplementation, and treatment response, and these relationships appear to be clinically useful in the treatment of SARS.     

Biodegradable,thermosensitive implant for approximating cylindrical structures: a preliminary study

A new invention, i.e., a biodegradable, thermosensitive hybrid gel composite in the form of a thin sheet, was used as an implant inside the rat and guinea pig to test its tissue reactions, degradation, and function as a bridging agent. Tissue tractions in subcutaneous tissue, in muscle, around a peripheral nerve, and around an artery were mild. Degradation made rapid progress, starting on the third day and completed in 2-3 weeks. The hybrid gel, when wrapped around the cut ends of a peripheral nerve or an artery, functioned well as a bridging tube. In the case of the cut nerve, regenerating fascicles crept through the tube which protected them from fibrosis. In the case of the cut artery, patency of flow was maintained, and arterial wall healing was complete in 2-3 weeks. The hybrid gel composite contracted at body temperature, thus holding well to body tissues. Its biodegradable and inert nature offers the potential for future use as a tissue wrap and bridging agent.     

Effects of inhaled ambient particulate matter on pulmonary antimicrobial immune defense

Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of <10 microm diameter (PM(10)). These epidemiological findings suggest that PM(10) may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms. To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed. The first examined the effects of a single inhalation exposure to concentrated ambient PM(2.5) (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae. The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 microg/m(3), could exacerbate an ongoing infection. Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S. pneumoniae. Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls. These studies demonstrate that a single exposure to ambient PM(2.5) compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals.     

ABCA4 sequence variants in Chinese patients with age-related macular degeneration or Stargardt's disease

ABCA4 gene sequence alterations cause Stargardt's disease (STGD) and may cause some age-related macular degeneration (AMD). We sought to shed light on these associations among Hong Kong Chinese by genotyping 140 AMD, 18 STGD and 95 normal control subjects for 15 ABCA4 exons which were reported to often contain AMD- or STGD-associated mutations. Sequence alterations R212H, T1428M, V1433I, T1572M, I2166M, IVS6-5T>G and IVS33+1G>T were found in AMD patients. T1428M and R2040X occurred in STGD patients. Control subjects displayed all the above missense alterations but no splicing or nonsense changes. Therefore, ABCA4 splicing mutations may be associated with a small proportion of AMD cases.     

Tarsal-conjunctival disease associated with Wegener's granulomatosis

OBJECTIVE: To describe the clinical characteristics of tarsal-conjunctival disease in a cohort of patients with Wegener's granulomatosis (WG). DESIGN: Retrospective, case-controlled study. PARTICIPANTS: The medical records of 82 consecutive WG patients who underwent an eye examination between January 1996 and June 2002 at the National Institutes of Health were reviewed. METHODS: Details of the ophthalmic examination, results of medical therapy, and histopathologic analysis results were recorded. Tarsal-conjunctival disease was defined by (1). conjunctival hyperemia and granuloma formation, areas of necrosis, or active fibrovascular changes in the tarsus or conjunctiva, or (2). evidence of inactive fibrovascular scar. The association of tarsal-conjunctival disease with major organ system involvement was assessed using Bayesian methods. MAIN OUTCOME MEASURES: The occurrence and clinical characteristics of tarsal-conjunctival disease in a cohort of patients with WG and associations with major organ system involvement. RESULTS: Tarsal-conjunctival disease occurred in 13 of 82 patients (16%) with WG examined over a 6.5-year period. The palpebral surface of the upper lid was involved most commonly, showing conjunctival hyperemia in seven patients, granulomatous lesions in three patients, tarsal-conjunctival necrosis in four patients, active fibrovascular proliferation in six patients, and inactive fibrous scar tissue in seven patients. Histopathologic analysis of eyelid biopsy specimens showed granulomatous inflammation, focal necrosis, and areas of occlusive vasculitis in the tarsus and conjunctiva. In reviewing the patterns of organ involvement in patients with and without tarsal-conjunctival disease, the association of subglottic stenosis and nasolacrimal duct obstruction with tarsal-conjunctival disease showed a high probability of clinical significance. CONCLUSIONS: Tarsal-conjunctival disease, a previously uncommon finding in patients with WG, was characterized by inflammation of the palpebral conjunctiva and tarsus followed by a fibrovascular proliferation and scar formation. Because of the important association of tarsal-conjunctival disease with subglottic stenosis, which can progress and lead to laryngeal obstruction and respiratory failure, patients with tarsal-conjunctival disease should be referred to an otolaryngologist for evaluation.     

A polymeric micellar carrier for the solubilization of biphenyl dimethyl dicarboxylate

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1 K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialy-sis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1 K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (>5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.