Effects of timing of oral calcium administration on milk production in high-producing early-lactation Holstein cows.

Supplementation of oral Ca via blanket administration of an oral Ca bolus at 0 and 24 h after calving has shown limited success in increasing production and minimizing adverse health events. Recent evidence that reductions in blood Ca at 4 d in milk (DIM) are more closely associated with negative outcomes than hypocalcemia at 0 to 24 h postpartum might explain this lack of Ca bolus efficacy. Therefore, our primary objective was to explore the effect of delayed oral Ca bolus supplementation on milk production, with secondary objectives of exploring the effects on disease incidence and postpartum blood Ca dynamics. We conducted a randomized controlled trial on multiparous Holstein cows (n = 998) from 4 herds in New York. At calving, cows were randomly assigned to 1 of 3 treatment groups: (1) control, no supplemental Ca at or around parturition (CON; n = 343); (2) conventional bolus, an oral Ca bolus containing 43 g of Ca at calving and 24 h later (BOL-C; n = 330); or (3) delayed bolus, an oral Ca bolus containing 43 g of Ca at 48 and 72 h after calving (BOL-D; n = 325). We created generalized linear mixed models to analyze differences in milk yield for the first 10 wk of lactation and serum total Ca (tCa) at 1 and 4 DIM between treatment groups; multivariable Poisson regression models were used to analyze adverse event outcomes (metritis, displaced abomasum, herd removal, or a combination of one or more of the 3) in the first 30 DIM. Milk yield increased by week and was not affected by treatment. However, a treatment by parity group interaction for milk yield showed that BOL-D cows in the third parity produced more milk than third-parity BOL-C or CON cows (BOL-D = 52.0 kg/d, 95% confidence interval [50.6, 53.4] kg/d, BOL-C = 47.9 [46.3, 49.5] kg/d, CON = 49.8 [48.2, 51.2] kg/d). The incidence of adverse health events was similar between treatments (BOL-D = 3.7%, BOL-C = 3.7%, CON = 3.6%). Serum tCa was lower at 1 than 4 DIM, and we detected no difference in tCa between treatment groups. Our findings suggest that delaying oral Ca bolus supplementation has limited influence on blood Ca concentrations but may be beneficial to cohorts of cows as a targeted prophylactic supplement to support milk production.

Three-dimensional analysis of the surface registration accuracy of electromagnetic navigation systems in live endoscopic sinus surgery.

BACKGROUND: Studies on the performance of surface registration with electromagnetic tracking systems are lacking in both live surgery and the laboratory setting. This study presents the efficiency in time of the system preparation as well as the navigational accuracy of surface registration using electromagnetic tracking systems. METHODOLOGY: Forty patients with bilateral chronic paranasal pansinusitis underwent endoscopic sinus surgery after undergoing sinus computed tomography scans. The surgeries were performed under electromagnetic navigation guidance after the surface registration had been carried out on all of the patients. The intraoperative measurements indicate the time taken for equipment set-up, surface registration and surgical procedure, as well as the degree of navigation error along 3 axes. RESULTS: The time taken for equipment set-up, surface registration and the surgical procedure was 179 +- 23 seconds, 39 +- 4.8 seconds and 114 +- 36 minutes, respectively. A comparison of the navigation error along the 3 axes showed that the deviation in the medial-lateral direction was significantly less than that in the anterior-posterior and cranial-caudal directions. CONCLUSION: The procedures of equipment set-up and surface registration in electromagnetic navigation tracking are efficient, convenient and easy to manipulate. The system accuracy is within the acceptable ranges, especially on the medial-lateral axis.

Intracellular zinc release-activated ERK-dependent GSK-3ß-p53 and Noxa-Mcl-1 signaling are both involved in cardiac ischemic-reperfusion injury.

Oxidative stress and nitrosative stress are both suggested to be involved in cardiac ischemia-reperfusion (I/R) injury. Using time-lapse confocal microscopy of cardiomyocytes and high-affinity O(2)(-•) and Zn(2+) probes, this study is the first to show that I/R, reactive oxygen species (ROS), and reactive nitrogen species (RNS) all cause a marked increase in the [O(2)(-•)](i), resulting in cytosolic and mitochondrial Zn(2+) release. Exposure to a cell-penetrating, high-affinity Zn(2+)(i) chelator, TPEN, largely abolished the Zn(2+)(i) release and markedly protected myocytes from I/R-, ROS-, RNS-, or Zn(2+)/K(+) (Zn(2+)(i) supplementation)-induced myocyte apoptosis for at least 24 h after TPEN removal. Flavonoids and U0126 (a MEK1/2 inhibitor) largely inhibited the myocyte apoptosis and the TPEN-sensitive I/R- or Zn(2+)(i) supplement-induced persistent extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, dephosphorylation of p-Ser9 on glycogen synthase kinase 3ß (GSK-3ß), and the translocation into and accumulation of p-Tyr216 GSK-3ß and p53 in, the nucleus. Silencing of GSK-3ß or p53 expression was cardioprotective, indicating that activation of the ERK-GSK-3ß-p53 signaling pathway is involved in Zn(2+)-sensitive myocyte death. Moreover, the ERK-dependent Noxa-myeloid cell leukemia-1 (Mcl-1) pathway is also involved, as silencing of Noxa expression was cardioprotective and U0126 abolished both the increase in Noxa expression and in Mcl-1 degradation. Thus, acute upstream Zn(2+)(i) chelation at the start of reperfusion and the use of natural products, that is, flavonoids, may be beneficial in the treatment of cardiac I/R injury.

Comparison of the once-daily levofloxacin-containing triple therapy with the twice-daily standard triple therapy for first-line Helicobacter pylori eradication: a prospective randomised study.

BACKGROUND/AIMS: Simple compound of Helicobacter pylori eradication therapy may improve drug compliance of patients. The aims of this study were to compare the efficacy and tolerability of a simple combination containing levofloxacin 7-day once-daily with standard twice-daily triple therapy. PATIENTS AND METHODS: This was a prospective, randomised, open-label trial. A total of 189 consecutive patients diagnosed with peptic ulcer and H. pylori infection were enrolled. Patients were randomly divided into two groups: LEC group--levofloxacin 500 mg, esomeprazole 40 mg and clarithromycin 500 mg once daily for 7 days; AEC group--amoxicillin 1 g, esomeprazole 40 mg and clarithromycin 500 mg twice daily for 7 days. RESULTS: There were 90 patients in the LEC group and 99 patients in the AEC group. By intention-to-treat and per-protocol analysis, the H. pylori eradication rate was 78.9% [71/90; 95% confidence interval (CI), 70.3-87.5%] and 83.5% (71/85; 95% CI, 75.5-91.6%) respectively, in the LEC group; and 74.8% (74/99; 95% CI, 66.0-83.5%) and 86.0% (74/86; 95% CI, 78.6-93.5%) respectively, in the AEC group. The incidence and tolerability of side effects were similar between these two groups. CONCLUSION: The efficacy and tolerability of once-daily levofloxacin-containing triple therapy are equal to those of the standard twice-daily triple therapy in this study. However, none of the treatment regimens evaluated achieved enough eradication efficacies to be considered as a recommendable first-line treatment.

Elucidating therapeutic effects on patients with hepatocellular carcinoma and main portal vein thrombosis.

BACKGROUND/AIMS: The survival duration for patients diagnosed with hepatocellular carcinoma (HCC) with main portal vein thrombosis (MPVT) was usually less than 3 months. The aim of this study is to elucidate whether treatment can prolong the survival for such patients. METHODOLOGY: Retrospectively we analyzed the clinical features and outcomes of 63 patients with HCC and MPVT over a 7-year period. Three therapeutic modalities--transcatheter arterial chemotherapy (TAC) with or without radiotherapy (RT), and systemic chemotherapy--were applied. RESULTS: The patients were divided into two groups: 34 (54%) patients were treated, while the remaining 29 (46%) were not. Multivariate analysis revealed that Child-Pugh class, Okuda stage for HCC and the presence of treatment were the principal factors to predict survival. The survival was significantly longer in treated patients than those untreated both in the Child-Pugh class A or B patients. Significantly longer survival is evident in patients treated by TAC combing RT compared to those underwent TAC alone, systemic chemotherapy or no treatment. CONCLUSIONS: The survival of Child-Pugh class A or B patients can be extended by the use of an appropriate therapeutic modality. TAC combined with RT did the best benefit to prolong survival in such patients.

Study of prostaglandin receptors in mitochondria on apoptosis of human lung carcinoma cell line A549.

PGs (prostaglandins) are synthesized through the cyclo-oxygenase (COX-1 and -2) pathway in a variety of cells in response to various physiological stimuli. All cells require at least one pathway for apoptosis, and mitochondrial play a central role in regulation of apoptosis. In a previous study, incubation of A549 cells with NS-398 (a COX-2-specific inhibitor) induced apoptosis and inhibited cell proliferation, and the concentrations of different PGs between various cellular compartments were found to be changed. To determine whether PG receptors are involved in this regulation, Western-blot analyses were performed specific for PGE(2) (EP receptors) and PGF(2alpha) (FP receptor) receptors, which were expressed in A549 cells. Western-blot analysis revealed that mitochondria that were isolated from A549 cells expressed EP receptors (EP2, EP3 and EP4), whereas FP receptors were undetectable. EP receptors (EP1, EP3 and EP4) and FP receptors were detected from A549 cell membrane. These results suggest that the change of PG production in A549-cells-induced cancer cell apoptosis might be related to the different expressions of EP and FP receptors in cell and mitochondrial membrane.

Reactivation of hepatitis C virus superinfection in a patient seropositive for hepatitis B e antigen.

During the course of chronic hepatitis B virus (HBV) infection, a patient seropositive for hepatitis B e antigen experienced four episodes of acute hepatic necroinflammation. Serum HBV-DNA concentration elevated immediately before the first and third exacerbations, whereas serum hepatitis C virus (HCV) RNA was detected during the second and fourth exacerbations. The nucleotide sequences of HCV hypervariable region derived from samples of the two exacerbations were identical. Interestingly, "de novo" seroconversion of anti-HCV antibody (Abbott HCV EIA 3.0) followed by reversion occurred in both the second and fourth exacerbations with low sample/cutoff ratios. Immunoblot analysis using a line-immunoassay (Inno-LIA HCV Ab III) revealed a single positive band (C1) developing after the second exacerbation. These data indicate that the second exacerbation in this patient was caused by newly acquired acute HCV superinfection, whereas the fourth exacerbation was likely due to reactivation of the previous HCV infection. Recognition of such a case suggests that the presence of de novo seroconversion of anti-HCV may indicate either reactivation or acute superinfection of HCV in a patient seropositive for hepatitis B e antigen.

Kainic acid-induced neurotrophic activities in developing cortical neurons.

Using primary cultured cortical neurons from embryonic rat brains, we elucidated an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainic acid (KA) receptor-mediated neuroprotective mechanism through actions of nerve growth factor (NGF) in developing neurons. Neurotoxicity of KA in early days in vitro neurons was quite low compared with the mature neurons. However, pretreatment with anti-NGF antibody or TrkA inhibitor AG-879 profoundly raised KA toxicity. Furthermore, KA stimulation resulted in an increase of TrkA expression and phosphorylation, which was blocked not only by the AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and AG-879, but also by the phospholipase C inhibitor U73122 and the intracellular calcium chelator BAPTA. A study of polyphosphoinositide turnover showed that KA-stimulated phospholipase C (PLC) activity was directly triggered by the AMPA/KA receptor activity, but not by the activity of TrkA or other excitatory amino acid receptor subtypes. Sources of KA-increased intracellular calcium levels were contributed by both extracellular calcium influx and intracellular calcium release and were partially sensitive to guanosine 5'-O-(2-thiodiphosphate). These results indicate that in developing cortical neurons, activation of AMPA/KA receptors by KA may induce expression, followed by activation of TrkA via PLC signaling and intracellular calcium elevation and hence increase reception of NGF on KA-challenged neurons. A G protein-coupled AMPA/KA receptor may be involved in these metabotropic events for neuronal protection.

Multiple lymphomatous polyposis of the gut: case report.

Multiple lymphomatous polyposis (MLP) is an uncommon type of primary non-Hodgkin's gastrointestinal B-cell lymphoma characterized by the presence of multiple lymphomatous polyps along the gut. We present a patient with MLP in which the involvement was unusually widespread. The diagnosis was confirmed by the typical polyposis lesion, histology, phenotyping and clinical presentations. A 68-year-old man had a large mass at the ileocecal valve as well as multiple polyps along the whole digestive tract. At the time of diagnosis, lymphoma had involved bone marrow, peripheral blood, spleen, prostate and peripheral lymph nodes. The patient received 8 courses of chemotherapy with no remission. He died of pneumonia 11 months after diagnosis. Clinically, the diagnosis may be confused with epithelial polyps; and histologically, the diagnosis must be distinguished from benign lymphoid proliferations as well as other types of lymphoma. The prognosis for patients with MLP is relatively poor (the median survival is usually less than 3 years).

Superinfection with hepatitis C virus in hemodialysis patients with hepatitis B surface antigenemia: its prevalence and clinical significance in Taiwan.

A survey of hepatitis B surface antigen (HBSAG) and antibodies against hepatitis C virus (anti-HCV) in 173 patients undergoing hemodialysis in Taiwan revealed that 15 (9%) patients were positive for both HBSAG and anti-HCV, 106 (61%) were positive for anti-HCV alone, and 14 (8%) were positive for HBSAG alone. Most HBSAg positivity was acquired before the onset of hemodialysis. Anti-HCV positivity, however, was mainly acquired via the hemodialysis procedure. Patients with dual markers were younger (43.7 +/- 3.3 years old, p = 0.0274), had the longest period on hemodialysis (6.6 +/- 1.3 years, p < 0.001), and more severe liver dysfunction. When compared with those who were negative for both markers, patients with both HBSAG and anti-HCV had an increased incidence of chronicity (5/15 vs. 2/38; p < 0.05), ultrasonographic cirrhosis (5/15 vs. 1/38; p < 0.05), and clinical decompensation (2/15 vs. 0/38; p < 0.05). Their risk for developing ultrasonographic cirrhosis and clinical decompensation was also greater than that of patients with anti-HCV alone (5/15 vs. 8/106 and 2/15 vs. 2/106; p < 0.05 for both). The presence of HBSAG alone, however, did not increase the incidence of liver dysfunction. The presence of anti-HCV alone was only associated with a greater elevation of serum alanine aminotransferase (44.2 +/- 5.5 vs. 19.1 +/- 2.5 U/l; p < 0.05) and an increased incidence of chronicity (30/106 vs. 2/38; p < 0.05). Our results indicate that a high prevalence of HCV superinfection impose a significant risk on a large population of HBSAG-positive hemodialysis patients in Taiwan. As the coexistence of anti-HCV and HBSAG is associated with more severe liver dysfunction, it is urgent to devise effective methods to prevent HCV circulation in a hemodialysis environment-especially in a hepatitis B virus endemic area such as Taiwan.

Assessment of four rapid urease test systems for detection of Helicobacter pylori in gastric biopsy specimens.

An in vitro experiment and an in vivo clinical trial were both performed in order to assess the efficacy of four biopsy urease test systems, including one commercial kit, Temmler CUT test (Temmler Pharma, Marburg, Germany), for the rapid detection of Helicobacter pylori. We first evaluated four rapid urease test systems by inoculating bacterial suspensions of different concentrations into urea-containing media and observing the color change at room temperature. We found that the CUT test was superior in vitro to the other three urease test systems. As was expected, the lower the concentration of the inoculum, the slower was the color change and the fewer were the positive results noted. The minimal concentration of H. pylori for a positive urease test at 24 h was 1000-10,000 colony-forming units/ml in 1 drop of bacterial suspension inoculated. We then evaluated four biopsy urease test systems for the rapid diagnosis of H. pylori infection in antral and fundal mucosa biopsy specimens of 37 patients undergoing upper gastrointestinal endoscopy. All four test systems were 100% specific when compared with culture. In 69 culture-positive biopsy specimens, the CUT test was not only more sensitive (72%) than the other three systems (42%, 51%, and 45%, respectively), but also gave the fastest reaction by detecting more culture-positive biopsy specimens after 3 h of incubation at room temperature. The differences were statistically significant.

[Biliary ascariasis].

From January 1982 to September 1987, ten diagnosed cases of biliary ascariasis were collected among 8,160 cases who were admitted for biliary tract diseases in our hospital. It represented an incidence of 0.12% in our hospital. In our series, the patients' ages ranged from 33 to 68 years old, with a female predominances. The clinical impression on admission were those of biliary tract stone, infection or pancreatitis. Signs and symptoms of biliary ascariasis were abdominal pain, fever, jaundice, vomiting of round worms and distended gallbladder. Laboratory findings disclosed leukocytosis, mildly elevated alkaline phosphatase, transaminase and bilirubin. There was a relatively high incidence of positive bile culture for bacteria. The reliable diagnostic tools for biliary ascariasis were abdominal real-time ultrasonography and endoscopic retrograde cholangiopancreatography (ERCP). They yielded a diagnostic rate of 40% and 87.5% respectively in our series. The principles of management of biliary ascariasis were conservative treatments including intravenous fluids, nasogastric decompression, antibiotics and antihelmintic agents. Other treatments that were also tried included endoscopic removal of round worms through a T-tube, or nasobiliary drainage. Surgery was considered when there were signs of complications, such as uncontrolled sepsis or suppurative cholangitis. The prognosis of biliary ascariasis was good if patients were diagnosed and treated properly. Regular follow-up with antihelmintic agents is also recommended to avoid reinfection.

Comparison of four different methods for detection of Helicobacter pylori from gastric biopsies.

Helicobacter pylori are commonly found colonizing the gastric mucosa of different populations. Its presence may be important in the pathogenesis of gastritis and peptic ulcer disease. The detection rates vary widely depending upon the diagnostic methods applied. In this study, multiple gastric biopsies were taken from the fundal and antral mucosa of 25 patients during endoscopy. In one patient, the procedure was repeated about two months after the initial biopsy. A total of 52 sets of specimens were obtained. One sample from each site was used to make imprint smear and tissue section. The other sample was used for microbiological culture and rapid urease test. An association between histological confirmed chronic gastritis (both active and inactive) and the morphological diagnosis of H. pylori by tissue sections was found in all of the 26 cases (52 specimens). There was an excellent concordance (96.2%) between the morphological diagnosis of H. pylori in the Gram-stained imprint smears and the tissue sections. There was a good concordance (86.5%) between the histology and the bacterial culture. Interestingly, a different species of gastric campylobacter-like organism with similar morphological appearance was also cultivated. The results of rapid urease test are unsatisfactory because urease was detected in less than 10% of culture-positive biopsies after 1 hour and 71.1% after 24 hours. In summary, culture and histology are complementary to each other. The combination of both is the "gold standard" for confirming the presence of H. pylori. As for rapid diagnosis, the Gram-stained imprint smears are shown to give satisfactory results.

Experience with major hepatic resections for hepatocellular carcinoma.

Nine major hepatic resections for hepatocellular carcinoma were performed during a period of 2 years and 4 months. HBsAg was positive in six patients, preoperative serum alpha-fetoprotein was more than 20 ng/ml in 5 patients, and liver cirrhosis was present in four patients. Two patients presented with spontaneous rupture of hepatocellular carcinoma. The great value of ultrasonography is stressed as an emergency diagnostic tool in any patient with an acute abdomen without obvious cause. There was no operative mortality or morbidity among this series of patients. All but one patient with a ruptured hepatoma are alive without evidence of disease 3-31 months after liver resection. These encouraging operative results made the authors willing to adopt an aggressive policy toward the surgical treatment of hepatocellular carcinoma.

Different implications of stigmata of recent hemorrhage in gastric and duodenal ulcers.

A prospective study was conducted to evaluate the prognostic value of stigmata of recent hemorrhage in patients with bleeding peptic ulcer. Of 193 patients suffering from peptic ulcer bleeding identified by emergency gastrointestinoscopy, 52 patients were found to have bleeding gastric ulcer (spurt 5, active oozing 9, fresh clot 11, black clot 17, protruding vessel 4, and clear base without stigmata 6); the other 141 had bleeding duodenal ulcer (spurt 5, active oozing 26, fresh clot 43, black clot 23, protruding vessel 15, and clear base without stigmata 31). Patient with continuous bleeding or rebleeding was grouped as unstable bleeders. The rate of unstable bleeders was 39.1% (continuous bleeding 23.9% and rebleeding 15.2%) in patients with gastric ulcer, compared to 9.0% (4.5% and 4.5%) in duodenal ulcer (P less than 0.001). The unstable bleeder rate of ulcers with spurt, active oozing, clot, and protruding vessel was 80%, 44%, 35.7%, and 0%, respectively, in patients with bleeding gastric ulcer; and 33.3%, 19.2%, 6%, and 0%, respectively, in patients with bleeding duodenal ulcer. The data suggest that the stigmata of recent hemorrhage, excluding protruding vessel, has prognostic significance in bleeding gastric ulcer but less in bleeding duodenal ulcer.