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At least 433 records · Page 24Linked to original sources
PubMed1985

Detection of hepatitis B virus DNA in serum and relation with the IgM class anti-HBc titers in hepatitis B virus infection.

Sera from four groups of patients wtih different serologic markers of HBV infection were examined for HBV DNA using molecular hybridization technique and for IgM class anti-HBc using an ELISA based on the antibody capture principle. Results of HBV DNA assay were generally in good agreement with the presence of HBeAg. However, HBV DNA was found in 13% of anti-HBe+ sera and in one patient with anti-HBc as a sole marker. IgM anti-HBc was detected at high titers in acute hepatitis B patients and was also present during the "window-period." This marker was also found, though less frequently when other markers for HBV infectivity were absent, in chronic hepatitis B patients and healthy carriers. From these findings we conclude that the HBV DNA assay provides a reliable method of detecting the infectious agent, particularly in anti-HBe+ sera and sera with anti-HBc as a sole marker. The assay for IgM anti-HBc is useful for establishing the diagnosis of recent infection in patient with anti-HBc as a sole marker, and during acute hepatitis with very high aminotransferase values, a condition in which HBV DNA may be undetectable.

Acute Disease↗
PubMed1985

Absence of detectable hepatitis B virus DNA in sera and liver of chimpanzees with non-A, non-B hepatitis.

The risk of hepatitis B infections has been reduced by screening of blood donors for hepatitis B surface antigen (HBsAg). However, recipients remain at significant risk of developing post-transfusion hepatitis. Studies have shown that non-A, non-B hepatitis virus(es) are responsible for the majority of post-transfusion hepatitis infections. In spite of many efforts, these non-A, non-B hepatitis viruses have not yet been identified. Epidemiological studies, however, suggest that non-A, non-B hepatitis shares many features with hepatitis B. Recently, Wands et al [1982] showed, in chimpanzees infected with non-A, non-B hepatitis agents, the presence of antigenemia or viremia by radioimmunoassay with monoclonal antibodies directed toward distinct determinants of HBsAg and by molecular hybridization analysis. They suggested that non-A, non-B hepatitis agents may be related, but distinct variant(s) of hepatitis B virus (HBV). In this study, five chimpanzees were inoculated with three different agents that have been shown to transmit non-A, non-B hepatitis. The following inocula were used (I) a factor VIII preparation kindly provided by D.W. Bradley, (II) acute phase serum from a chimpanzee infected with the F strain kindly provided by A.J. Zuckerman, and (III) a DS-antigen serum previously shown by us to transmit non-A, non-B hepatitis [Duermeyer et al, 1983]. All chimpanzees developed a rise in transaminase levels between 8 and 10 weeks after inoculation. None of the chimpanzees was positive for any markers of HBV infection. No evidence was obtained of infection with hepatitis A, cytomegalovirus, or Epstein-Barr virus. One chimpanzee developed chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatitis B pre-S1 and pre-S2 proteins: clinical significance and relation to hepatitis B virus DNA.

Pre-S proteins may have an important role in virus assembly and virus entry into the host cell. The presence of pre-S proteins in serum has also been thought to correlate with active viral replication. To investigate whether pre-S proteins in serum might have additional diagnostic and/or predictive value for liver sequelae in HBV infection, sera from six different serological groups of patients with HBV markers (total number 363) and different manifestations of liver histology were examined for the presence of pre-S1 and pre-S2 proteins using micro-ELISAs. Pre-S1 and pre-S2 proteins were detected significantly more often in HBV-DNA-positive than in HBV-DNA-negative sera from HBsAg carriers. However, pre-S1 and pre-S2 proteins were also found in HBV-DNA-negative HBsAg carriers irrespective of serum HBeAg/anti-HBe or liver histologic findings. These results suggest that the presence of the pre-S1 and or pre-S2 proteins in serum either does not seem to reflect the presence of active viral replication and active liver disease or pre-S proteins are more readily detectable than HBeAg and HB-DNA as measured by a dot-blot technique. Furthermore, the presence of pre-S proteins in serum is strongly correlated with that of HBsAg.

Chronic Disease↗
PubMed1991

Surrogate markers are not useful for identification of HCV carriers in chronic hemodialysis patients.

Several diagnostic hepatitis C assays have been developed for the detection of antibodies to different antigens of the virus. This virus is the major cause of non-A, non-B hepatitis. Seventy-nine patients undergoing chronic hemodialysis and/or hemofiltration were tested for the presence of anti-HCV antibodies (anti-C-100-3 antibodies and anti-core antibodies), anti-hepatitis B core antibodies (anti-HBc), and aminotransferases (ALT). Seven patients were positive by one or more of the anti-HCV enzyme linked immunoassays (EIAs), while HCV-RNA was detectable in only four patients. These four patients had at least one, but not necessarily the same, positive anti-HCV EIA. HCV-RNA was not detected in patients who had no antibodies as determined by all six anti-HCV EIAs. All patients with a marker for HCV infection had persistent normal levels of transaminases. Three patients had elevated ALT values without a marker for HCV infection and suffered from hepatitis B virus infection. Anti-HBc was detected in 27/72 patients without any marker and in four patients with a marker of HCV infection. However, HCV-RNA was detectable in only one of these four anti-HBc positive patients. It is concluded that surrogate markers (anti-HBc and serum transaminases) are not useful for identification of HCV carriers in chronic hemodialysis patients.

Biomarkers↗
PubMed1993

Confirmation of hepatitis C virus antibody in blood donors.

Of 103,203 donations collected in Scotland and Northern Ireland over a 3-month period and screened for HCV antibody by Ortho or Abbott second-generation ELISAs, 340 were found repeatedly reactive. Supplementary testing with RIBA-2 resulted in 77 being classified as positive, 130 as indeterminate, and 133 as negative. PCR analysis of the positives and indeterminates indicated viraemia in 65 (84%) of the positives and 7 (5.5%) of the indeterminates. To determine if PCR analysis could be eliminated or reduced by further serological testing, all RIBA-2 positives and indeterminates were tested by UBI and Wellcozyme ELISAs and Innolia and RIBA-3 immunoblots. All RIBA-2 positives with bands to more than 1 gene product were detected in all 4 systems, but > 60% of RIBA-2 indeterminates were negative in those tests that contain either recombinant antigens or synthetic peptides derived independently from those used by Ortho/Abbott tests. A comparison of data from the 79 reactive with the core (c22) region revealed only 16 samples reactive in all 4 systems as well as Ortho and Abbott. These 16 included all 6 of the PCR positives in the 79 c22 indeterminate samples. ELISAs and immunoblots using independently derived antigens can offer a useful method of screening out nonspecific reactions in Ortho or Abbott ELISAs, hence reducing the need for PCR testing. Some caution is required as all such tests do not contain identical mixes of antigenic material.

Antigens, Viral↗
PubMed1994

Hepatitis C virus-RNAs in plasma and in peripheral blood mononuclear cells of hemophiliacs with chronic hepatitis C: evidence for viral replication in peripheral blood mononuclear cells.

Hemophiliacs who have been exposed to unheated and/or dry heated pooled clotting factor concentrates are at high risk of chronic hepatitis C. Although the mechanism and site of hepatitis C virus (HCV) replication are not yet known, HCV is thought to replicate through a complementary negative RNA strand, as has been shown for flaviviruses. The detection of negative RNA strands has therefore been regarded as a marker of replication. We investigated the prevalence of HCV-RNA and of negative HCV-RNA strands in peripheral blood mononuclear cells (PBMC) and plasma of hemophiliacs. Forty-three of 47 patients studied (91%) had anti-HCV antibodies and in 36 patients HCV-RNA was detectable in PBMC. In one group of 20 patients negative HCV-RNA strands were present in PBMC and 10 of these patients also had negative HCV-RNA strands in plasma. In another group of nine patients HCV-RNA was detected in PBMC, although cDNA synthesis was carried out in the absence of primers. Only in two of these nine patients negative and positive HCV-RNA strands were demonstrated specifically in PBMC using a modified reverse transcription step. If the presence of negative HCV-RNA strands can be considered as marker of viral replication, the findings indicate that HCV can replicate in PBMC. Furthermore, in certain patients it is impossible to use the currently available technique to detect selectively positive or negative HCV-RNA strands.

Adolescent↗
PubMed1995

Hepatitis C virus genotypes in Belgian hemophiliacs.

Hemophiliacs who have been exposed to unheated and/or dry heated pooled clotting factor concentrates are at a high risk of chronic hepatitis C. Serum HCV-RNA was measured by reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 58 hemophiliacs positive for anti-HCV antibodies, HCV-RNA was detected in 55 patients. Based on the results of PCR positivity, HCV genotyping was carried out using genotype specific probes and the dot blot hybridization assay: 2 patients were found to be infected with type 1a (3.6%), 31 patients with type 1b (56.4%), 8 patients with type 2 (14.6%), 6 patients with type 3 (10.9%), 1 patient with type 4, and 7 patients with double infection (12.7%). As compared to a control group of 105 nonhemophilia patients with chronic hepatitis C, HCV genotype 1b was found predominant in both groups. However, double infection with two HCV types as well as a relatively high prevalence of infection with type 2 and type 3 were found in hemophiliacs.

Adolescent↗
PubMed2004

Excess hospital admissions for pneumonia, chronic obstructive pulmonary disease, and heart failure during influenza seasons in Hong Kong.

It is widely held that Southern China is a hypothetical influenza epicentre for the emergence of pandemic influenza viruses. However, influenza is perceived as a relatively unimportant infection in this part of the world compared with western countries. Hong Kong is situated within the hypothetical epicentre and serves as a sentinel post for the region. In a retrospective study, the influenza-associated excess hospitalisations in a regional hospital for pneumonia, chronic obstructive pulmonary disease (COPD), heart failure, and asthma in persons aged > or = 65 years from 1998 to 2001 were each estimated by a model taking into consideration the confounding effect of other respiratory viral infections, seasonal factors, time trends, and weather and pollution indices. In the regression models, influenza activity is an independent significant factor affecting admission rates for pneumonia, COPD, and heart failure but not that for asthma. The variations in hospital admissions for pneumonia, COPD, and heart failure explained by influenza activity were 38.9, 7.5, and 45.6%, respectively. The adjusted rates of excess influenza-associated hospital admissions for the three diagnoses combined amounted to 58.5, 20.0, 29.2, and 13.4 per 10,000 populations aged > or = 65 years in 1998, 1999, 2000, and 2001, respectively. In conclusion, influenza activity is associated significant excess hospital admissions among elderly aged 65 or above in Hong Kong, comparable to the data reported in Western countries. The findings support a wider application of annual influenza vaccination in this region.

Aged↗
PubMed2005

Quantitative Structure-Pharmacokinetic Relationships for drug distribution properties by using general regression neural network.

Quantitative Structure-Pharmacokinetic Relationships (QSPkR) have increasingly been used for developing models for the prediction of the pharmacokinetic properties of drug leads. QSPkR models are primarily developed by means of statistical methods such as multiple linear regression (MLR). These methods often explore a linear relationship between the pharmacokinetic property of interest and the structural and physicochemical properties of the studied compounds, which are not applicable to those agents with nonlinear relationships. Hence, statistical methods capable of modeling nonlinear relationships need to be developed. In this work, a relatively new kind of nonlinear method, general regression neural network (GRNN), was explored for modeling three drug distribution properties based on diverse sets of drugs. The three properties are blood-brain barrier penetration, binding to human serum albumin, and milk-plasma distribution. The prediction capability of GRNN-developed models was compared to those developed using MLR and a nonlinear multilayer feedforward neural network (MLFN) method. For blood-brain barrier penetration, the computed r(2) and MSE values of the GRNN-, MLR-, and MLFN-developed models are 0.701 and 0.130, 0.649 and 0.154, and 0.662 and 0.147, respectively, by using an independent validation set. The corresponding values for human serum albumin binding are 0.851 and 0.041, 0.770 and 0.079, and 0.749 and 0.089, respectively, and that for milk-plasma distribution are 0.677 and 0.206, 0.224 and 0.647, and 0.201 and 0.587, respectively. These suggest that GRNN is potentially useful for predicting QSPkR properties of chemical agents.

Algorithms↗
PubMed1976

Development of a stable sublingual nitroglycerin tablet II: formulation and evaluation of tablets containing povidone.

Stable and pharmaceutically elegant sublingual nitroglycerin tablets were formulated using povidone to retard volatilization of the drug. Formulation and processing variables were investigated to produce an acceptable product. A blend of two grades of povidone, of different degrees of cross-linkage and water solubility, provided stable tablets which exhibited rapid disintegration. Directly compressed sublingual tablets made in this study retained over 80% of the initial nitroglycerin when exposed to the atmosphere at room temperature for 2 months. The direct compression tablets are of good appearance and low friability, and the formulation is readily compressed without problems. An interesting relationship among the hardness, disintegration time, and compaction pressure is described.

Drug Compounding↗
PubMed1978

Improved GLC determination of plasma nitroglycerin concentrations.

A specific and quantitative assay for determining nanogram levels of nitroglycerin in plasma was developed. The method involves stabilization of the drug in plasma with silver nitrate, followed by multiple extraction using purified hexane. Isosorbide dinitrate is added as the internal standard. The hexane extract is subsequently concentrated and injected into a glass column packed with 3% SP-2401 on 100--120-mesh Supelcoport at 140 degrees. A 63Ni-electron-capture detector gives a linear response over the range of 0.1--50 ng of nitroglycerin/ml of rat plasma. From spiked samples, the procedure gave a recovery of about 90%. There was little or no interference from the isomeric glyceryl dinitrates and endogenous compounds in rat or human plasma.

Animals↗
PubMed1978

Pharmacokinetics of nitroglycerin in rats.

The plasma nitroglycerin levels obtained after intracardial (0.7 mg/kg), oral (7 mg/kg), and topical (7--14 mg/kg) doses of nitroglycerin in rats are reported. Nitroglycerin followed essentially one-compartment kinetics after intracardial administration, showing a mean half-life of about 4 min and a mean apparent volume of distribution of about 3 liters/kg. After oral drug administration, "flip-flop" kinetics were evident. The mean oral bioavailability was determined to be 1.6%, firmly supporting the contention that nitroglycerin is extensively metabolized during first passage through the liver. Under the experimental conditions studied, no detectable levels of nitroglycerin were observed after topical application.

Administration, Oral↗
PubMed1979

Combined chemoimmunotherapy and radiation therapy of inflammatory breast carcinoma.

Thirty-two patients with a diagnosis of primary inflammatory breast carcinoma were treated with combination chemoimmunotherapy consisting of 5-fluorouracil, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (FAC) plus BCG followed by radiation therapy. This group of patients was compared to a group of 32 consecutive historical controls treated with radiation therapy alone. The estimated mean disease-free interval for the FAC-BCG group was 16 months, compared to 9 months for the radiation therapy alone group (P less than 0.01). The estimated median survival for the FAC-BCG treated group was 24 months, compared to 18 months for the radiation therapy alone group (P = less than 0.03). The combined modality approach consisting of chemoimmunotherapy and radiation therapy significantly improved the disease-free interval and survival of patients with inflammatory breast carcinoma.

Adult↗
PubMed1979

Adjuvant chemoimmunotherapy following regional therapy for isolated recurrences of breast cancer (stage IV NED).

A combination of 5-fluorouracil, Adriamycin, cyclophosphamide, and BCG (FAC-BCG) was evaluated as adjuvant treatment in breast cancer patients following surgical excision and/or radiation of first site of recurrent disease. In a group of 68 patients treated with FAC-BCG, the estimated proportion remaining free of disease at 2 years from first recurrence was 69%, compared to 24% in 60 historical control patients (P less than 0.01). Estimated 2-year survival rate from first recurrence was 85% for the FAC-BCG patients and 78% for the controls (P = 0.07). This regimen has significantly prolonged the disease-free interval from the first recurrence, but additional follow-up is needed to determine its effect on long-term survival.

Antineoplastic Agents↗
PubMed1979

Chemoimmunotherapy with or without oophorectomy in premenopausal patients with advanced breast cancer.

Ninety-eight premenopausal patients with stage IV breast cancer were treated with chemoimmunotherapy alone, or with combination oophorectomy-chemoimmunotherapy either simultaneously (chemoimmunotherapy within four weeks of oophorectomy) or sequentially (delayed chemoimmunotherapy until evidence of progressive disease or no response to oophorectomy). The chemoimmunotherapy consisted of a three-drug combination of Adriamycin, cyclophosphamide, and 5-fluorouracil or Ftorafur; immunotherapy consisted of either oral levamisole, BCG by scarification, or a combination of both. Forty patients underwent simultaneous oophorectomy-chemoimmunotherapy, with a response rate of 85% and a median duration of response of 25 months. Response rate of 69% and a median duration of response of 16.6 months was observed with the 29 patients who received sequential oophorectomy-chemoimmunotherapy. Another 29 patients were treated with chemoimmunotherapy alone and achieved a response rate of 87% and a median duration of response of 11.8 months. Though there were no significant differences in the response rate, patients treated with chemoimmunotherapy alone had a significantly shorter median duration of response (P less than 0.05). This would suggest that oophorectomy in combination with chemoimmunotherapy is the most favorable treatment modality for premenopausal patients with advanced metastatic breast cancer.

BCG Vaccine↗
PubMed1980

Sarcoma of the stomach: clinicopathologic study of 43 cases.

The records of 43 patients with histologically proved primary gastric sarcoma treated at M. D. Anderson Hospital and Tumor Institute between 1945 and 1975 were reviewed. Weight loss, abdominal pain, and hematemesis or melena were the most common symptoms, and palpable epigastric mass was the most common physical sign. Ninety-five percent of the gastric tumors were leiomyosarcomas. The median survival time and the five-year survival for the 29 patients who had curative gastrectomy were 33 months and 38%, respectively. Morphologic and histologic factors that adversely influenced the length of disease-free interval and survival following curative surgery included 1) primary tumor 8 cm or greater in diameter, 2) tumor extension to serosa of the stomach, and 3) low grade of differentiation of the primary tumor. Seventy-seven percent of recurrences in patients with curative tumor resection occurred within two years of resection of the primary. Of the 17 patients with advanced disease who received chemotherapy, two (15%) had objective tumor regression of greater a median survival time of eight months for patients who failed to respond. New approaches that may improve the results of treatment of gastric sarcoma are discussed.

Female↗
PubMed1981

Combination chemoimmunotherapy with FAC-BCG for metastatic breast cancer: the impact of CMF maintenance chemotherapy.

In an attempt to prolong the durations of remission and survival of patients with advanced breast cancer treated with the FAC-BCG protocol, we modified the CMF maintenance combination by increasing the dose of all three drugs and administering them intravenously. Eighty-five evaluable patients treated with this new regimen were compared with a recent historical control group of 105 evaluable patients treated with FAC-BCG and a lower-dose, oral CMF maintenance program. The overall (70% and 76%) and complete (16% and 19%) response rates were identical in these two groups. The median times to progression for all patients entered were similar too (13 months for both groups.). The durations of response were 17 months (PO-CMF) and 14 months (IV-CMF), not significantly different (P = .16). The durations of survival of the two treated groups were also very similar. After the administration of intensive FAC induction therapy, a high-dose, intravenous CMF maintenance program appears no better than a low-dose oral regimen. Other drug combinations consisting entirely of drugs not used in the induction regimen might be better choices for maintenance treatment

Administration, Oral↗