Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.

PURPOSE: The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. METHODS: A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. RESULTS: Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. CONCLUSION: Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.

Detection of low-frequency oscillations in renal blood flow.

Detection of the low-frequency (LF; approximately 0.01 Hz) component of renal blood flow, which is theorized to reflect the action of a third renal autoregulatory mechanism, has been difficult due to its slow dynamics. In this work, we used three different experimental approaches to detect the presence of the LF component of renal autoregulation using normotensive and spontaneously hypertensive rats (SHR), both anesthetized and unanesthetized. The first experimental approach utilized a blood pressure forcing in the form of a chirp, an oscillating perturbation with linearly increasing frequency, to elicit responses from the LF autoregulatory component in anesthetized normotensive rats. The second experimental approach involved collection and analysis of spontaneous blood flow fluctuation data from anesthetized normotensive rats and SHR to search for evidence of the LF component in the form of either amplitude or frequency modulation of the myogenic and tubuloglomerular feedback mechanisms. The third experiment used telemetric recordings of arterial pressure and renal blood flow from normotensive rats and SHR for the same purpose. Our transfer function analysis of chirp signal data yielded a resonant peak centered at 0.01 Hz that is greater than 0 dB, with the transfer function gain attenuated to lower than 0 dB at lower frequencies, which is a hallmark of autoregulation. Analysis of the data from the second experiments detected the presence of approximately 0.01-Hz oscillations only with isoflurane, albeit at a weaker strength compared with telemetric recordings. With the third experimental approach, the strength of the LF component was significantly weaker in the SHR than in the normotensive rats. In summary, our detection via the amplitude modulation approach of interactions between the LF component and both tubuloglomerular feedback and the myogenic mechanism, with the LF component having an identical frequency to that of the resonant gain peak, provides evidence that 0.01-Hz oscillations may represent the third autoregulatory mechanism.

Electrohydraulic pump-driven closed-loop blood pressure-regulatory system.

In this paper, we describe our design for a new electrohydraulic (EH) pump-driven renal perfusion pressure (RPP)-regulatory system capable of implementing precise and rapid RPP regulation in experimental animals. Without this automated system, RPP is manually controlled via a blood pressure clamp, and the imprecision in this method leads to compromised RPP data. This motivated us to develop an EH pump-driven closed-loop blood pressure regulatory system based on flow-mediated occlusion using the vascular occlusive cuff technique. A closed-loop servo-controller system based on a proportional plus integral (PI) controller was designed using the dynamic feedback RPP signal from animals. In vivo performance was evaluated via flow-mediated RPP occlusion, maintenance, and release responses during baseline and ANG II-infused conditions. A step change of -30 mmHg, referenced to normal RPP, was applied to Sprague-Dawley rats with the proposed system to assess the performance of the PI controller. The PI's performance was compared against manual control of blood pressure clamp to regulate RPP. Rapid RPP occlusion (within 3 s) and a release time of approximately 0.3 s were obtained for the PI controller for both baseline and ANG II infusion conditions, in which the former condition was significantly better than manual control. We concluded that the proposed EH RPP-regulatory system could fulfill in vivo needs to study various pressure-flow relationships in diverse fields of physiology, in particular, studying the dynamics of the renal autoregulatory mechanisms.

Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection.

A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.

A rare cause of intestinal perforation in an extreme low birth weight infant--gastrointestinal mucormycosis: a case report.

We report an extreme low birth weight infant with gastrointestinal mucormycosis (GM) mimicking necrotizing enterocolitis on day 15 of age. Emergency laparotomy confirmed ileal perforations. Subsequently, tissue histology confirmed GM. This is the most premature infant who survived after GM and is the third reported neonatal survivor in English literature.

Maternal diclofenac sodium ingestion and severe neonatal pulmonary hypertension.

We describe a case of severe pulmonary hypertension and transient right-sided hypertrophic cardiomyopathy in a neonate, caused by premature closure of ductus arteriosus after short-term maternal use of diclofenac sodium (Voltaren). In view of this associated complication, diclofenac sodium should be avoided during pregnancy. In addition, maternal diclofenac sodium ingestion should be suspected if a newborn develops severe pulmonary hypertension and/or right-sided hypertrophic cardiomyoptathy with closed ductus arteriosus.

Isolation of Helicobacter pylori from vomitus in children and its implication in gastro-oral transmission.

OBJECTIVE: The route of transmission of Helicobacter pylori (H. pylori) is unclear. Gastro-oral transmission via contaminated vomitus has been proposed as an important mode of transmitting H. pylori, especially in children. This pilot study attempted to isolate H. pylori from the vomitus of children. METHODS: Children presenting for evaluation with gastroenteritis-associated vomiting were studied. Fresh vomitus samples were collected for detection of H. pylori by bacteriological culture and polymerase chain reaction, (PCR). A rapid, whole blood test was used to determine the H. pylori status of patients. RESULTS: A total of 18 children with mean age of 6 yr were studied; four had a positive serology test. Among these four children, H. pylori was isolated from vomitus by culture in one child and by PCR in two. An 18-month-old girl with negative serology had H. pylori detected in vomitus by PCR. Six months later, she had seroconversion confirmed, suggesting that she had an acute H. pylori infection on initial presentation. CONCLUSIONS: This is the first study reporting successful isolation of H. pylori from naturally produced vomitus. The result implies that transmission of H. pylori infection by vomitus, especially in children, is possible.

Use of chopsticks for eating and Helicobacter pylori infection.

Epidemiological data suggests that ethnic groups using chopsticks for eating have a higher prevalence of H. pylori infection. This study investigated the carriage of H. pylori in chopsticks after eating. Used chopsticks and saliva were collected from asymptomatic individuals whose H. pylori status was determined by [13C]urea breath test and serology. Both the saliva specimens and chopsticks were cultured and processed by polymerase chain reaction (PCR) for the detection of H. pylori. Furthermore, chopsticks used by hospital staff in the cafeteria were pooled for the detection of H. pylori by bacteriologic culture and PCR. Sixty-nine volunteers were recruited in the first study and 45 (65%) were diagnosed to have H. pylori infection. While all cultures were negative, H. pylori was detected by PCR in the saliva from 15 (33%) infected subjects and in the chopsticks from one (2%). Among the 12 sets of pooled chopstick-washing studied, H. pylori was detected by PCR in two sets. This study showed that H. pylori was rarely detected in chopsticks after eating and hence, the risk of contracting this infection via the use of chopsticks is low.

A male newborn with colonic atresia and total colonic aganglionosis.

A case of colonic atresia (CA) and aganglionosis is presented, which is probably the tenth in the English literature. The boy presented on day 3 of life with delayed passage of meconium, milk intolerance, and progressive abdominal distension. A barium enema study was complicated by barium peritonitis. Emergency peritoneal lavage was done and the intestinal obstruction was relieved by a proximal defunctioning ileostomy; type III CA (Grosfeld classification) was identified. The proximal atretic end was the blind-ending caecum and the distal atretic end commenced in the splenic area as a microcolon extending to the pelvis and replacing the normal colon. Total colonic aganglionosis (TCA) was confirmed by biopsies. This is the first case in the literature of TCA with CA documented before any attempts at colonic resection and anastomosis were made. This association highlights the recommendation for biopsy of the micro-colon and rectum when Type III CA (Grosfeld classification) is encountered in a newborn. The infant underwent a cholecystectomy and Duhamel-Martin operation at 14 months that was complicated by abdominal wound dehiscence; the ileostomy was closed at 22 months of age.

False-negative biopsy urease test in bleeding ulcers caused by the buffering effects of blood.

OBJECTIVES: A false-negative biopsy urease test (BUT) is common in Helicobacter pylori-associated bleeding peptic ulcers. Although blood in the stomach is thought to interfere with the biopsy urease test, the underlying mechanism remains unknown. This in vitro experiment sought to identify the blood component(s) that interfere with the biopsy urease test, and delineate the mechanism of inhibition. METHODS: The modified Hazell's microtiter test was used to detect the urease activity of H. pylori. A positive result was indicated by a color change of the pH indicator, bromothymol blue, at 630 nm. Human whole blood, sera with and without anti-H. pylori antibody, electrolytes, and enzymes were incubated with H. pylori to identify the blood component(s) causing the inhibition of urease activity. In addition, any interference of the pH color indicator was tested by adding different concentrations of serum albumin to the urease reagent that contained a fixed quantity of ammonia in the absence of H. pylori. RESULTS: The color change of the microtiter urease test was significantly reduced by blood (p < 0.0001), regardless of the presence of anti-H. pylori antibody. Electrolytes and serum enzymes did not interfere with the urease test. The color change of the pH indicator was progressively suppressed by higher concentrations of serum albumin. CONCLUSIONS: Blood adversely affects the performance of the BUT. This is mediated by the buffering effect of serum albumin on the pH indicator, rather than by a direct inhibition on the urease activity.