On the asymptotic evolution of finite energy Airy wave functions.

In general, there is an inverse relation between the degree of localization of a wave function of a certain class and its transform representation dictated by the scaling property of the Fourier transform. We report that in the case of finite energy Airy wave packets a simultaneous increase in their localization in the direct and transform domains can be obtained as the apodization parameter is varied. One consequence of this is that the far-field diffraction rate of a finite energy Airy beam decreases as the beam localization at the launch plane increases. We analyze the asymptotic properties of finite energy Airy wave functions using the stationary phase method. We obtain one dominant contribution to the long-term evolution that admits a Gaussian-like approximation, which displays the expected reduction of its broadening rate as the input localization is increased.

Spatiotemporal dispersion and wave envelopes with relativistic and pseudorelativistic characteristics.

A generic nonparaxial model for pulse envelopes is presented. Classic Schrödinger-type descriptions of wave propagation have their origins in slowly-varying envelopes combined with a Galilean boost to the local time frame. By abandoning these two simplifications, a picture of pulse evolution emerges in which frame-of-reference considerations and space-time transformations take center stage. A wide range of effects, analogous to those in special relativity, then follows for both linear and nonlinear systems. Explicit demonstration is presented through exact bright and dark soliton pulse solutions.

Helmholtz solitons at nonlinear interfaces.

Reflection and refraction of spatial solitons at dielectric interfaces, accommodating arbitrarily angles of incidence, is studied. Analysis is based on Helmholtz soliton theory, which eliminates the angular restriction associated with the paraxial approximation. A novel generalization of Snell's law is discovered that is valid for collimated light beams and the entire angular domain. Our new theoretical predictions are shown to be in excellent agreement with full numerical simulations. New qualitative features of soliton refraction and limitations of previous paraxial analyses are highlighted.

Spatial Kerr soliton collisions at arbitrary angles.

The theory of spatial Kerr solitons is extended to colliding beams that are neither almost-exactly copropagating nor almost-exactly counterpropagating. Our new Helmholtz formalism yields results that are consistent with the inherent symmetry of the collision process and that are not predicted by existing paraxial descriptions. Full numerical and approximate analytical results are presented. These show excellent agreement. In particular, Kerr solitons are found to be remarkably robust under nonparaxial collisions.

Fresnel diffraction and fractal patterns from polygonal apertures.

Two compact analytical descriptions of Fresnel diffraction patterns from polygonal apertures under uniform illumination are detailed. In particular, a simple expression for the diffracted field from constituent edges is derived. These results have fundamental importance as well as specific applications, and they promise new physical insights into diffraction-related phenomena. The usefulness of the formulations is illuminated in the context of a virtual source theory that accounts for two transverse dimensions. This application permits calculation of fractal unstable-resonator modes of arbitrary order and unprecedented accuracy.

Helmholtz-Manakov solitons.

A different spatial soliton-bearing wave equation is introduced, the Helmholtz-Manakov (HM) equation, for describing the evolution of broad multicomponent self-trapped beams in Kerr-type media. By omitting the slowly varying envelope approximation, the HM equation can describe accurately vector solitons propagating and interacting at arbitrarily large angles with respect to the reference direction. The HM equation is solved using Hirota's method, yielding four different classes of Helmholtz soliton that are vector generalizations of their scalar counterparts. General and particular forms of the three invariants of the HM system are also reported.

Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.

BACKGROUND: The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood. AIMS: To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB. PATIENTS AND METHODS: Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay. RESULTS: Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative. CONCLUSIONS: The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Spontaneous optical fractal pattern formation.

We report, for the first time, spontaneous nonlinear optical spatial fractals. The proposed generic mechanism employs intrinsic nonlinear dynamics both to generate an initial pattern seed and to fill out structure across decades of spatial scale. We demonstrate this in one of the simplest of nonlinear optical systems, composed of a Kerr slice and a single-feedback mirror. In this case, the smallest pattern scales are limited by either the optical wavelength or the diffusion length of the medium photoexcitation. The dimension characteristics of these particular fractals are also derived.

Factors influencing the development of Barrett's epithelium in the esophageal remnant postesophagectomy.

BACKGROUND: Barrett's esophagus results from chronic reflux of both acid and bile. Reflux of gastric and duodenal contents is facilitated through the denervated stomach following esophagectomy, but the development of Barrett's changes in this model and the relationship to gastric and esophageal physiology is poorly understood. AIMS: To document the development of new Barrett's changes, i.e., columnar metaplasia or specialized intestinal metaplasia (SIM) above the anastomosis, and relate this to the recovery of gastric acid production, acid and bile reflux, manometry, and symptoms. PATIENTS AND METHODS: Forty-eight patients at a median follow-up of 26 months (range = 12-67) postesophagectomy underwent endoscopy with biopsies taken 1-2 cm above the anastomosis. The indication for esophagectomy had been adenocarcinoma (n = 27), high-grade dysplasia (n = 2), and squamous cell cancer (n = 19). Physiology studies were performed in 27 patients and included manometry (n = 25), intraluminal gastric pH (n = 24), as well as simultaneous 24-hour esophageal pH (n = 27) and bile monitoring (n = 20). RESULTS: Duodenogastric reflux increased over time, with differences between patients greater than and less than 3 years postesophagectomy for acid (p = 0.04) and bile (p = 0.02). Twenty-four patients (50%) developed columnar metaplasia and of these 13 had SIM. The prevalence of columnar metaplasia did not relate to the magnitude of acid or bile reflux, to preoperative neoadjuvant therapies, or to the original tumor histology. The duration of reflux was most significant, with increasing prevalence over time, with SIM in 13 patients at a median of 61 months postesophagectomy compared with 20 months in the 35 patients who were SIM-negative (p < 0.006). Supine reflux correlated with symptoms. CONCLUSIONS: The development of Barrett's epithelium is frequent after esophagectomy, is time-related, reflecting chronic acid and bile exposure, and is not specific for adenocarcinoma or the presence of previous Barrett's epithelium. This model may represent a useful in vivo model of the pathogenesis of Barrett's metaplasia and tumorigenesis.

Helmholtz dark solitons.

A general dark-soliton solution of the Helmholtz equation (with defocusing Kerr nonlinearity) that has on- and off-axis, gray and black, paraxial and Helmholtz solitons as particular solutions, is reported. Modifications to soliton transverse velocity, width, phase period, and existence conditions are derived and explained in geometrical terms. Simulations verify analytical predictions and also demonstrate spontaneous formation of Helmholtz solitons and transparency of their interactions.

Transvenous liver biopsy via the femoral vein.

AIM: To study the safety, effectiveness and diagnostic value of transvenous forceps biopsy of the liver in 54 patients with coagulopathy, gross ascites or morbid obesity and suspected liver disease in whom percutaneous liver biopsy was contraindicated. MATERIAL AND METHODS: Forceps biopsy of the liver via the femoral vein was attempted in 54 adult patients with advanced liver disease of unknown aetiology who had coagulation disorders (41 cases), gross ascites (11 cases) or morbid obesity (two cases). In each patient two to six biopsies (average four) were taken using a radial jaw forceps inserted via the right or left femoral vein. RESULTS: The procedure was successful in 53 cases. Hepatic vein catheterization failed in one patient. Adequate liver tissue for diagnosis was obtained in 84% of cases. One patient developed delayed haemorrhage at 12 h from a capsular leak that was undetected during the biopsy procedure. This patient required blood transfusions and laparotomy to control bleeding. There were no deaths in the 53 patients studied. Transient minor chest and shoulder pain was encountered during sheath insertion into a hepatic vein in 23 patients. Three patients developed a femoral vein haematoma, which resolved with conservative treatment. CONCLUSION: Transvenous liver biopsy via the femoral vein is another safe, effective, simple alternative technique of biopsy when the percutaneous route is contraindicated.

Management of multiple burn casualties in a high volume ED without a verified burn unit.

The objective of the study was to evaluate the effectiveness of triage, treatment, and transfer interventions on multiple burn casualties managed in a high volume ED that does not have a verified in-hospital burn unit. The charts of 11 male patients injured in a 1999 foundry explosion and brought to Baystate Medical Center (BMC), a level I trauma center, were reviewed. All patients sustained deep partial and full thickness burns. The injury severity score (ISS) ranged from 9 to 75. Five patients had total body surface area (TBSA) burns of 10% to 50% and 6 patients had TBSA burns of 70% to 95%. Transfer times from the scene to BMC ranged from less than 5 minutes to 22 minutes. All 11 were initially triaged, resuscitated, and evaluated at BMC. Of the 9 patients transferred to verified burn units, 8 were intubated, 6 of 6 had negative abdominal ultrasounds, 4 had undergone escharatomies, and 1 had undergone bronchoscopy before transfer. Nine critically injured burn patients with ISS of 9 to 75 were transferred from BMC to verified burn units. For 8 of these patients, the average time from triage, evaluation, and treatment to transfer was 2 hours. The ninth patient was initially admitted overnight then promptly transferred after re-evaluation of his hand burns indicated a need for more specialized care. Two of 9 transferred patients, both with ISS of 75 died. Although 7 other patients had prolonged and complex courses, none of their subsequent complications were referable to missed injuries from this transferring facility. The resources and expertise of a high volume ED without an in-hospital burn unit can be effectively used in the initial resuscitation and treatment of multiple burn casualties. Coordinated responses among emergency medicine, trauma, anesthesia, and nursing personnel are instrumental to the rapid triage, resuscitation, and treatment of critically injured burn patients. Future disaster planning should incorporate a clearly demarcated, ED command center led by an easily identifiable "captain of the ship," as well as more accurate patient identification systems and improved communications with family members.

Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease.

BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory bowel disease. AIM: A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease. METHODS: Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading. RESULTS: The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events. CONCLUSION: Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.

The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C.

BACKGROUND & AIMS: In hepatitis C infection, several studies have examined the role of the major histocompatibility complex (MHC) in determining outcome, with variable results. To clarify the importance of MHC, we examined class II DR and DQ antigens in a homogenous cohort of women exposed to hepatitis C genotype 1b from a single inoculum. METHODS: Of 243 participants, 95 had spontaneous viral clearance and 148 are chronically infected. The frequencies of HLA class II DR and DQ antigens were compared between the 2 groups and between liver biopsy findings of 145 chronically infected subjects. RESULTS: DRB1*0101 and DQB1*0501 alleles were more frequent in subjects who sustained viral clearance than in chronically infected subjects (32.3% and 36.8% vs. 8.8% and 14.2%, respectively; P = 0.002). DRB1*03011 and DQB1*0201 occurred more frequently in chronically infected subjects than in those who cleared the virus (41.5% and 42.6% vs. 16.7% and 15.8%, respectively; P = 0.001). Both DRB1*03011 and DQB1*0201 were significantly less frequent in those with higher inflammatory scores on liver biopsy. CONCLUSIONS: We show that in a homogenous cohort of women infected with the same hepatitis C virus, several HLA antigens are associated with either viral clearance or persistence. This suggests a strong role for host immunogenetic factors in determining outcome in hepatitis C infection.

Guided versus blind liver biopsy for chronic hepatitis C: clinical benefits and costs.

BACKGROUND/AIMS: Our objectives were: (1) to assess the clinical benefits and costs of performing ultrasound-guided liver biopsy with an automated needle compared to blind biopsy with a conventional Trucut needle in patients with chronic hepatitis C; (2) to compare the histological yield of automated needles with Trucut needles. METHODS: We prospectively studied 166 patients with hepatitis C virus who underwent either ultrasound-guided biopsy using automated ASAP needles or blind biopsy using conventional Trucut needles. Both groups were matched for age, sex, cirrhosis, needle gauge and operator experience. Patient tolerance, complications and histological adequacy were assessed. In a separate in vitro study, we assessed the histological adequacy of liver biopsy specimens obtained using automated and Trucut needles from 10 fresh autopsy cases. RESULTS: Ultrasound-guided biopsy caused significantly less biopsy pain (36.4% vs. 47.3%; p < 0.0001) and significantly less pain-related morbidity (1.8% vs. 7.7%, p < 0.05). Although, there was no significant difference in diagnostic yield between guided and blind biopsy (98% vs. 94%, p = 0.15), 3 blind biopsies (3.3%), including 2 which yielded extra-hepatic tissue, had to be repeated. The additional expense of performing guided liver biopsy with automated needles was 42 Irish Pounds per patient. In vitro, automated ASAP 15G needles provided liver specimens comparable to Trucut 15G needles and had the highest histopathologic score among the automated needles assessed. CONCLUSIONS: Even in the absence of major complications, ultrasound-guided liver biopsy with an automated needle in HCV patients is safer, more comfortable and only marginally more expensive than blind Trucut biopsy.

Excess-noise dependence on intracavity aperture shape.

In lasers with nonorthogonal eigenmodes the excess-noise factor K can be large, especially in unstable-cavity lasers with hard-edged intracavity apertures. To the best of our knowledge, we report the first detailed study of the dependence of K on aperture shape. Calculations and measurements of K for unstable-cavity lasers with variable-size apertures of triangular, square, pentagonal, hexagonal, octagonal, and rhomboid symmetries are summarized. It is shown that both the magnitude of K and its resonant behavior strongly depend on aperture shape and that many aspects of this dependence can be explained in terms of one-dimensional resonance lengths.

The development of hepatic granulomas following interferon-alpha2b therapy for chronic hepatitis C infection.

Hepatic granulomas have been detected in cases of chronic hepatitis C virus (CHCV) infection. Here we report upon three selected cases of CHCV infection who were treated with IFN alpha, in whom hepatic granulomas were absent on initial liver biopsies, but in whom granulomas developed following IFN alpha therapy. In one case, complete regression of these granulomas was noted 17 months following discontinuation of treatment, more strongly implicating IFN alpha in the aetiopathogenesis of such granulomas in this case. These findings suggest that IFN alpha may have a biological role in the pathogenesis of granulomatous liver disease in these patients. All three cases were poor/non-responders to IFN alpha, suggesting that the development of hepatic granulomas during IFN alpha therapy may be associated with a poor response to treatment.

Liver biopsy pathology in human immunodeficiency virus infection.

OBJECTIVES: To determine the hepatic changes in patients with human immunodeficiency virus (HIV) infection in Dublin and to assess the usefulness of liver biopsy in this condition. DESIGN: A consecutive series of liver biopsies was examined retrospectively and correlated with clinical findings. METHODS: A histological review was conducted of specimens from all patients who had undergone liver biopsy in a tertiary referral centre for HIV-infected patients in Dublin. RESULTS: Thirty-nine liver biopsies were studied from 36 patients. Thirty-one (86%) showed pathological changes. Non-specific changes were most frequent, followed by viral-induced chronic hepatitis (15 cases). Acute hepatitis was documented in five and cirrhosis in four cases. Five biopsies performed for pyrexia of unknown origin (PUO) or suspected tuberculosis showed granulomas. Organisms were rarely identified (2) and bile duct changes were uncommon. CONCLUSIONS: Liver biopsy was useful in detecting primary hepatic pathology and, in some cases, the cause of PUO, but not useful in detecting opportunistic infections despite their known presence in other organs.

Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C.

This look-back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion-transmitted HCV infection acquired in the neonatal period. A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti-D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994-95; the past donations of five of the donors, who had received anti-D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994-95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined. Twenty-one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti-HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis. The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.