Surgical lung biopsy for the diagnosis of interstitial lung disease: a review of the literature and recommendations for optimizing safety and efficacy.

Making an accurate diagnosis of a specific type of interstitial lung disease (ILD) requires a structured and comprehensive approach that includes a complete patient history, careful physical examination, appropriate laboratory testing, and thoracic imaging. If invasive procedures are required, bronchoscopy with bronchoalveolar lavage (BAL) and/or endoscopic lung biopsy (ELB) can frequently establish a confident diagnosis. However, surgical lung biopsy (SLB) may be required to make a confident diagnosis. Because SLB may be associated with a significant risk of morbidity and mortality, we performed a comprehensive literature review of all available literature published in the English language that reported outcomes of surgical lung biopsy performed for the diagnosis of ILD. The overall 30-day mortality for open lung biopsy (OLB) was 4.3% versus 2.1% for video-assisted thorascopic surgery (VATS) biopsy, and non-lethal complications appeared to occur more frequently with OLB (18.1%) vs. VATS (9.6%) procedures. In addition to presenting the results of our comprehensive literature review on SLB for the diagnosis of ILD, we suggest an approach that minimizes risks to patients and optimizes the diagnostic utility of SLB when SLB must be performed to obtain a confident ILD diagnosis.

Use of Kv1.3 blockers for inflammatory skin conditions.

Recent results using animal models of inflammatory skin conditions have shown that blockers of the voltage-gated potassium channel, Kv1.3 hold great promise for clinical utility. Kv1.3 blockers act as immunosuppressants by modulating the various subsets of inflammatory T and B cells involved in autoimmune disorders. While peptidic inhibitors based on naturally occurring venoms demonstrate potent and selective Kv1.3 blockade, these require parenteral administration and may face potential immunogenicity problems. Small molecule blockers show considerable diversity, however selectivity over other Kv1-family channels has been difficult to achieve. More recent advances have added to the evidence that Kv1.3 channels are a suitable therapeutic target and that the development of novel and selective agents will herald new drugs for inflammatory skin disorders.

A new technique for the measurement of the dynamic evolution of surface tension.

We develop a novel technique which deduces the surface tension in air of a fluid as a function of surface age, beginning at age zero. The technique utilizes pointwise measurements of perpendicular free surface profiles of a steady oscillating jet corresponding to a discretization interval on the order of 0.1 ms. We implement the technique on constant-surface-tension test fluids (100% ethanol and 15% ethanol/85% water by volume) to demonstrate the extent to which the technique can qualitatively capture that the surface tensions of these fluids are constant in time, and quantitatively produce values of these constants consistent with static measurements. We then implement the technique on jets of two agricultural surfactant mixtures, Triton X-405 and Triton X-100, and quantitatively deduce the decay of surface tension as a function of surfactant concentration.

Spontaneous perforation of the right hepatic duct.

Spontaneous perforation of the biliary ductal system is a rare cause of peritonitis with a high morbidity and mortality rate. We present a case of an 80-year-old female who presented to the Emergency Department with acute onset abdominal pain and peritoneal signs. She was taken to the operating room for exploratory laparotomy and discovered to have a perforation of her right hepatic duct. Several risk factors were found to play a role in her biliary perforation: biliary calculi, infection, and vessel thrombosis. She underwent a cholecystectomy, choledochotomy with removal of gallstones, repair of the perforation, and placement of a T-tube. She had a prolonged recovery in the intensive care unit and was eventually discharged to a skilled nursing facility. We conclude that the management of this unique and highly fatal disease can be applied with an excellent outcome.

Activation of enteropathogenic Escherichia coli (EPEC) LEE2 and LEE3 operons by Ler.

Enteropathogenic Escherichia coli (EPEC) produces attaching and effacing lesions (AE) on epithelial cells. The genes involved in the formation of the AE lesions are contained within a pathogenicity island named the locus of enterocyte effacement (LEE). The LEE comprises 41 open reading frames organized in five major operons: LEE1, LEE2, LEE3, LEE4 and tir. The first gene of the LEE1 operon encodes a transcription activator of the other LEE operons that is called the LEE-encoded regulator (Ler). The LEE2 and LEE3 operons are divergently transcribed with overlapping -10 promoter regions, and gene fusion studies have shown that they are both activated by Ler. Deletion analysis, using lacZ reporter fusions, of the LEE2 and LEE3 promoters demonstrated that deletions extending closer to the LEE2 transcription start site than -247 bp lead to loss of activation by Ler, whereas only 70 bp upstream of the LEE3 transcription start site is required for Ler-mediated activation. We have purified Ler as a His-tagged protein and used it to perform DNA-binding assays with LEE2 and LEE3. We observed that Ler bound to a DNA fragment containing the -300 to +1 region of LEE2; however, it failed to bind to a DNA fragment containing the -300 to +1 region of LEE3, suggesting that Ler activates both operons by only binding to the regulatory region upstream of LEE2. The Ler-activatable LEE3:lacZ fusions extended to what would be -246 bp of the LEE2 operon. A lacZ fusion from the -300 to +1 region of LEE3 failed to be activated by Ler, consistent with our hypothesis that Ler activates the expression of LEE2 and LEE3 by binding to a region located downstream of the LEE3 transcription start site. DNase I footprinting revealed that Ler protected a region of 121 bp upstream of LEE2. Purified Ler mutated in the coiled-coil domain was unable to activate transcription and to bind to the LEE2 regulatory region. These data indicate that Ler may bind as a multimer to LEE2 and activate both divergent operons by a novel mechanism potentially involving changes in the DNA structure.

Xenogeneic patch closure of the small intestine: a novel approach to fistula management.

Previous work from our laboratory demonstrated the feasibility of utilizing placental-derived collagen tissue matrix (CTM) as a bowel wall substitute. We reasoned that this technique would also be suitable in managing intestinal fistulae. To test this hypothesis, we created a chronic cecal fistula in rats and randomly managed some with primary repair and others with CTM replacement. Leak rates, mortality, bursting pressures and histologic scores were similar, suggesting that a chronic fistula can be successfully managed with either a CTM or primary repair.

Quorum sensing controls expression of the type III secretion gene transcription and protein secretion in enterohemorrhagic and enteropathogenic Escherichia coli.

Enterohemorrhagic Escherichia coli O157:H7 and enteropathogenic E. coli cause a characteristic histopathology in intestinal cells known as attaching and effacing. The attaching and effacing lesion is encoded by the Locus of Enterocyte Effacement (LEE) pathogenicity island, which encodes a type III secretion system, the intimin intestinal colonization factor, and the translocated intimin receptor protein that is translocated from the bacterium to the host epithelial cells. Using lacZ reporter gene fusions, we show that expression of the LEE operons encoding the type III secretion system, translocated intimin receptor, and intimin is regulated by quorum sensing in both enterohemorrhagic E. coli and enteropathogenic E. coli. The luxS gene recently shown to be responsible for production of autoinducer in the Vibrio harveyi and E. coli quorum-sensing systems is responsible for regulation of the LEE operons, as shown by the mutation and complementation of the luxS gene. Regulation of intestinal colonization factors by quorum sensing could play an important role in the pathogenesis of disease caused by these organisms. These results suggest that intestinal colonization by E. coli O157:H7, which has an unusually low infectious dose, could be induced by quorum sensing of signals produced by nonpathogenic E. coli of the normal intestinal flora.

New assistive technology for passive standing.

The anesthetic skin of patients with spinal cord injuries makes these patients a high-risk population for burn injuries. Innovations in rehabilitation engineering can now provide the disabled with mechanical devices that allow for passive standing. Passive standing has been shown to counteract many of the effects of chronic immobilization and spinal cord injury, including bone demineralization, urinary calculi, cardiovascular instability, and reduced joint range of motion and muscular tone. This article will describe several unique assistive devices that allow for passive standing and an improvement in daily living for people with disabilities.

Polyethylene glycol-superoxide dismutase inhibits lipid peroxidation in hepatic ischemia/reperfusion injury.

BACKGROUND: Hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (OFR)-mediated lipid peroxidation--a process that can be measured through its byproducts, specifically malondialdehyde. The use of free radical scavengers can offer significant protection against OFR-induced liver injury. We hypothesize that a new potent OFR scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD), can inhibit OFR-mediated lipid peroxidation in hepatic ischemia/reperfusion injury. METHODS: Twelve male Sprague-Dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. PEG-SOD (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. Normal saline was given to the remaining six rats to be used as a control group. The right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured. RESULTS: A marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. Treatment with PEG-SOD prevented the rise in tissue malondialdehyde. The mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 +/- 6.35 and 1.70 +/- 3.65 nmol/g in the normal saline (control) and PEG-SOD groups, respectively. This difference was found to be statistically significant (P < 0.005) using Student's t-test. CONCLUSIONS: PEG-SOD can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting OFR-mediated lipid peroxidation.

ILAE-defined epilepsy syndromes in children: correlation with quantitative MRI.

PURPOSE: The role of quantitative magnetic resonance imaging (MRI) in evaluation of childhood epilepsy remains poorly defined, with minimal published data. Previous work from our center questioned the specificity of hippocampal asymmetry (HA) in an outpatient group whose epilepsy was defined by using clinical and interictal data only. By using childhood volunteer controls and defining epilepsy syndromes using video-EEG monitoring, we readdressed the utility of HA in differentiating mesial temporal lobe epilepsy (MTLE) from other partial and generalized epileptic syndromes in children. METHODS: Seventy children were enrolled; entry criteria were age younger than 18 years with predominant seizure type recorded on video-EEG telemetry with volumetric MRI in all cases. Thirty healthy child volunteers had volumetric MRI. Epilepsy syndrome classification was according to ILAE. RESULTS: Control data revealed symmetric hippocampi, mean smaller/larger ratio of 0.96 (0.95-0.97, 95% CI) with no gender or right/left predominance. Overall 23% of patients had significant HA. Mean hippocampal ratio for MTLE was 0.78 (95% CI, 0.70-0.86), significantly lower than controls and from all other epilepsy syndromes. HA was highly specific (85%) to the syndrome of MTLE. Other potential epileptogenic lesions were found in 27 (39%) patients, lowest yield in frontal and mesial temporal syndromes. Dual pathology was present in 10% of patients. There was no significant association between HA and risk factors. CONCLUSIONS: In this study, we found that HA in children with a well-defined epilepsy syndrome is highly sensitive and specific for MTLE. Whether this will correlate with surgical outcome, as in adults, is the subject of ongoing study.

Familial ring (19) chromosome mosaicism: case report and review.

Ring (19) chromosomal mosaicism has been identified in a 14-month-old girl referred for cytogenetic evaluation due to microcephaly and developmental delay with autistic-like mannerisms. An analysis of her peripheral blood lymphocytes showed a 46,XX,r(19) cell line in 119/121 of cells examined. Of the two remaining cells, one had a normal female chromosome complement and the other showed loss of one of the chromosome 19 homologs. Further analysis by fluorescence in situ hybridization using an all human telomere probe showed the presence of a single hybridization signal on the r(19) chromosome. Subsequent cytogenetic characterization of cells derived from the patient's phenotypically normal mother also demonstrated the presence of a ring 19 chromosome in 4/100 cells. The remaining cells had a normal female chromosome complement. These findings represent the first reported case of familial ring 19 mosaicism. The cytogenetic and clinical findings in these two individuals are discussed in relation to six previously reported cases of de novo ring chromosome 19 mosaicism.

Evaluation of a new external condom catheter system.

The purpose of this study was to perform a biomechanical performance study and a clinical trial on a new external condom catheter system. The biomechanical performance study demonstrated that the vented connector failed following exposure to urine for 14 days. In addition, angulation of the inlet adapter of anti-reflux valve of the urinary leg bag to an angle of 35 degrees (+/-5 degrees) caused complete obstruction of urinary flow. A clinical trial of the new condom catheter with its inner flap revealed twisting of the catheter that interrupted urinary flow in four of ten patients. This catheter twisting was not observed in condom catheters without inner flaps. Furthermore, this new system is not easily applied or removed by patients with neurosensory deficits or musculoskeletal weakness. Design modifications of the vent within the connection tubing, the anti-reflux valve in the collection bag, the condom catheter with its inner flap, as well as the leg bag attachments should remarkably improve the performance of this new urinary drainage system.