Intensive care unit family satisfaction survey.

OBJECTIVES: To examine the level of family satisfaction in a local intensive care unit and its performance in comparison with international standards, and to determine the factors independently associated with higher family satisfaction. DESIGN: Questionnaire survey. SETTING: A medical-surgical adult intensive care unit in a regional hospital in Hong Kong. PARTICIPANTS: Adult family members of patients admitted to the intensive care unit for 48 hours or more between 15 June 2012 and 31 January 2014, and who had visited the patient at least once during their stay. RESULTS: Of the 961 eligible families, 736 questionnaires were returned (response rate, 76.6%). The mean (± standard deviation) total satisfaction score, and subscores on satisfaction with overall intensive care unit care and with decision-making were 78.1 ± 14.3, 78.0 ± 16.8, and 78.6 ± 13.6, respectively. When compared with a Canadian multicentre database with respective mean scores of 82.9 ± 14.8, 83.5 ± 15.4, and 82.6 ± 16.0 (P<0.001), there was still room for improvement. Independent factors associated with complete satisfaction with overall care were concern for patients and families, agitation management, frequency of communication by nurses, physician skill and competence, and the intensive care unit environment. A performance-importance plot identified the intensive care unit environment and agitation management as factors that required more urgent attention. CONCLUSIONS: This is the first intensive care unit family satisfaction survey published in Hong Kong. Although comparable with published data from other parts of the world, the results indicate room for improvement when compared with a Canadian multicentre database. Future directions should focus on improving the intensive care unit environment, agitation management, and communication with families.

Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis.

The newly discovered member of the tumor necrosis factor superfamily, Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), has been identified as an apoptosis-inducing agent in sensitive tumor cells but not in the majority of normal cells, and hence it is of potential therapeutic application. However, many tumor cells are resistant to Apo2L/TRAIL-mediated apoptosis. Various chemotherapeutic drugs have been shown to sensitize tumor cells to members of the tumor necrosis factor family. However, it is not clear whether sensitization by drugs and sensitivity to drugs are related or distinct events. This study examined whether an Adriamycin-resistant multiple myeloma (MM) cell line (8226/Dox40) can be sensitized by Adriamycin (ADR) to Apo2L/TRAIL-mediated apoptosis. Treatment with the combination of Apo2L/TRAIL and subtoxic concentrations of ADR resulted in synergistic cytotoxicity and apoptosis for both the parental 8226/S and the 8226/Dox40 tumor cells. Adriamycin treatment modestly up-regulated Apo2L/TRAIL-R2 (DR5) and had no effect on the expression of Fas-associated death domain, c-FLIP, Bcl-2, Bcl(xL), Bax, and IAP family members (cIAP-1, cIAP-2, XIAP, and survivin). The protein levels of pro-caspase-8 and pro-caspase-3 were not affected by ADR, whereas pro-caspase-9 and Apaf-1 were up-regulated. Combination treatment with Apo2L/TRAIL and ADR resulted in significant mitochondrial membrane depolarization and activation of caspase-9 and caspase-3 and apoptosis. Because ADR is shown to sensitize ADR-resistant tumor cells to Apo2L/TRAIL, these findings reveal that ADR can still signal ADR-resistant tumor cells, resulting in the modification of the Apo2L/TRAIL-mediated signaling pathway and apoptosis. These in vitro findings suggest the potential application of combination therapy of Apo2L/TRAIL and subtoxic concentrations of sensitizing chemotherapeutic drugs in the clinical treatment of drug-resistant/Apo2L/TRAIL-resistant multiple myeloma.

Chemosensitization of human prostate carcinoma cell lines to anti-fas-mediated cytotoxicity and apoptosis.

Androgen ablation has been an effective treatment in patients with advanced prostate cancer. However, most treated patients develop hormonally resistant disease and do not respond to conventional chemotherapy. Immunotherapy against prostate cancer is an alternative approach in overcoming hormonal/drug-resistant prostate cancer. Cytotoxic immune lymphocytes kill target cells via the perforin/granzyme and the Fas-ligand (Fas-L) pathways. We hypothesize that tumor cells respond poorly to immunotherapy by developing resistance to killing by the Fas-L mechanism. This study investigated whether prostate tumor cells are sensitive to Fas-mediated killing. The human prostate carcinoma cell lines DU145, PC-3, and LnCAP were examined for their sensitivity to killing and apoptosis by the Fas-L agonist anti-Fas antibody and CTLs. All three lines moderately expressed the Fas antigen on the cell surface; however, all three lines were relatively resistant to cytotoxicity mediated by anti-Fas (CH-11) antibody. Pretreatment of DU145 and PC-3 with subtoxic concentrations of drugs followed by anti-Fas antibody resulted in synergistic cytotoxicity and apoptosis, whereas only an additive effect was obtained with LnCAP. Chemosensitization with drugs and anti-Fas was completely blocked by the addition of neutralizing anti-Fas antibody. The murine CTL hybridoma, PMMI, which kills only via the Fas-L pathway, was able to kill chemosensitized PC-3 and DU145 but not LnCAP cells. Furthermore, this cytotoxicity was blocked by anti-Fas neutralizing antibody. Chemosensitization of PC-3 and DU145 prostate tumor cells was not due to up-regulation of Fas-receptor antigen expression. Treatment of tumor cells with cisplatin did not down-regulate the antiapoptotic genes bcl-2, FAP-1, and c-myc. Further, there was no induction by cisplatin of Fas-L on the tumor cells, thus ruling out Fas/Fas-L-mediated autologous killing. These findings demonstrate that pretreatment of drug-resistant/CTL-resistant prostate DU145 and PC-3 tumor cells with subtoxic concentrations of certain chemotherapeutic drugs sensitizes the tumor cells to Fas-mediated cytotoxicity. These findings suggest that chemosensitization of tumor cells should optimize the response to immunotherapeutic interventions in the treatment of hormone-resistant/drug-resistant prostate cancer.

Selectivity of TRAIL-mediated apoptosis of cancer cells and synergy with drugs: the trail to non-toxic cancer therapeutics (review).

There have been many advances in the therapy of cancer following the introduction of cytotoxic chemotherapeutic drugs. Notable responses were observed in primary tumors and often in malignant metastatic tumors. However, one of the consequences of chemotherapy is the development/acquisition of drug-resistant phenotypes and the development of multiple drug resistance. The development of drug resistance remains a major obstacle in the treatment of such tumors and therefore, there is an obvious need for alternative approaches such as immune/gene therapy. The cloning of biologically active cytotoxic molecules has been considered as potential new therapeutics in the destruction of drug-resistant tumor cells. For instance, some members of the TNF-superfamily are characterized by their ability to inflict cell death upon binding to their cognate receptors. TNF-alpha was the first molecule to be tested for its anti-tumor activity, followed by Fas-ligand. These two molecules are efficient in killing a variety of tumor cells, however, they cause significant damage to normal tissues that result in life-threatening toxicities. Therefore, the search for a cytotoxic molecule that is selective for tumor cells has continued until the recently discovered new member of the TNF superfamily, namely TRAIL/APO-2L. TRAIL has been shown to be selectively cytotoxic in inducing apoptosis against tumor cells and has minimal or no toxicity against normal tissues, as examined both in vitro and in vivo in mice. Therefore, TRAIL is a new agent that has great potential for its in vivo anti-cancer effect, whether used alone or in combination with drugs. Studies from our laboratory have recently demonstrated that tumor cells that are resistant to TRAIL can be sensitized by subtoxic concentrations of drugs/cytokines and the sensitized tumor cells are significantly killed by TRAIL. This review describes the current status of research studies performed with TRAIL by other investigators as well as by our laboratory.

Engineering the microstructure and permeability of thin multilayer latex biocatalytic coatings containing E. coli.

The microstructure and permeability of rehydrated 20-100 microm thick partially coalesced (vinyl-actetate acrylic copolymer) SF091 latex coatings and a 118 microm thick model trilayer biocatalytic coating consisting of two sealant SF091 layers containing a middle layer of viable E. coli HB101 + latex were studied as delaminated films in a diffusion apparatus with KNO(3) as the diffussant. The permeability of the hydrated coatings is due to diffusive transport through the pore space between the partially coalesced SF091 latex particles. Coating microstructure was visualized by fast freeze cryogenic scanning electron microscopy (cryo-SEM). The effective diffusion coefficient of SF091 latex coatings (diffusive permeability/film thickness) was determined as the ratio of the effective diffusivity of KNO(3) to its diffusivity in water (D(eff)/D). Polymer particle coalescence was arrested by two methods to increase coating permeability. The first used glycerol with coating drying at 4 degrees C, near the glass transition temperature (T(g)). The second method used sucrose or trehalose as a filler to arrest coalescence; the filler was then dissolved away. D(eff)/D was measured as a function of film thickness; content of glycerol, sucrose, and trehalose; drying time; and rehydration time. D(eff)/D varied from 3 x 10(-4) for unmodified SF091 coatings to 6.8 x 10(-2) for coatings containing sucrose. D(eff)/D was reduced by the flattening of latex particles against the surface of the solid substrate, as well as by the presence of the colloid stabilizer hydroxyethylcellulose (HEC). When corrected for the flattened particle layer, D(eff)/D of HEC-free coatings was as high as 0.20, which agreed with the value predicted from analysis of cryo-SEM images of the coat surface. D(eff)/D decreased by one-half in approximately 5 days in rehydrated SF091 coatings, indicating that significant wet coalescence occurs after glycerol, sucrose, or trehalose are leached from the films. D(eff)/D of SF091 latex trilayer coatings containing viable E. coli HB101 cells decreased as cell loading was increased from 2.2 x 10(-2) for 64 g dry cell weight per liter of coat volume to 5 x 10(-3) for 151 g DCW/L of coat volume. The reduction in coating permeability with increasing cell loading is predicted by Maxwell's equation for D(eff)/D in periodic composites.

6-Hydroxydopamine induced catecholamine depletion and passive avoidance learning in rats.

Rats were injected with 6-hydroxydopamine either intracisternally, intraperitoneally, or both, in order to examine the effects of central vs. peripheral catecholamine depletion on a step-down passive avoidance task. All rats acquired the response at the end of the five asquisition trials but the rates of acquisition of the drug-treated groups were siginificantly different from the control group. No significant difference in the performance results were observed between groups during the extinction period. These findings failed to confirm the hypothesis that an intact central and/or peripheral catecholaminergic systems may be necessary for the acquisition and extinction of a step-down passive avoidance response. In addition, this study also showed that plasma corticosterone levels in the rats depleted of central or peripheral catecholamine did not differ significantly from each other after passive avoidance training.

The comparative impact of video-consultation on neurosurgical health services.

This study evaluated the impact of telemedicine technology on the provision of neurosurgical health services. We focused on the differences between the use of real time audio-visual teleconferencing and teleradiology versus conventional telephone consultations in the referral of neurosurgical patients from a large district general hospital. All patients requiring emergency neurosurgical consultation were included for randomization into telephone consultation only (Mode A), teleradiology and telephone consultation (Mode B) and video-consultation (Mode C). Measures of effectiveness included diagnostic accuracy and adverse events during the transfer and Glasgow Outcome Score. In a 10-month period, 327 patients were recruited and randomized into the study: the male/female ratio was 2:1 and the number of patients required to be transferred to the neurosurgical unit was 125 (38%). There was a trend towards a more favourable outcome in the video-consultation mode (44%, Mode C), versus teleradiology (31%, Mode B), versus telephone consultation (38%, Mode A). The interim data of this prospective randomized trial suggests that video-consultation may have a favourable impact on emergency neurosurgical consultations.

Delays by patients, emergency physicians, and surgeons in the management of acute appendicitis: retrospective study.

OBJECTIVES: To compare the contributions of patients, emergency physicians, and surgeons in the delay of diagnosis and treatment of appendicitis, and the effects of delay on disease stage and complication rate. DESIGN: Retrospective study. SETTING: Accident and emergency department of a district public hospital, Hong Kong. PATIENTS: All patients undergoing emergency appendectomy between August 1998 to September 1999. MAIN OUTCOME MEASURES: Patient delay in presentation, emergency physician delay in hospital admission, and surgeon delay in performing the operation; operative findings; and postoperative complications. RESULTS: Of 158 patients undergoing emergency operation, 14 had no pathological diagnosis and four had a diagnosis other than that of acute appendicitis. Of the 140 pathologically confirmed cases of appendicitis, the mean emergency patient delay was greater in advanced appendicitis than it was in simple appendicitis (42.0 hours versus 24.9 hours; P<0.005). The mean emergency physician delay in advanced appendicitis was also greater than it was in simple appendicitis (17.9 hours versus 5.8 hours; P<0.05). The difference in the mean surgeon delay in simple (10.9 hours) and advanced (16.3 hours) appendicitis, however, was not significant. The mean emergency physician delay showed a significant association with the postoperative complication rate (P=0.05). The delay was mainly because of a failure to diagnose the condition and admit the patient at the first visit to the accident and emergency department (22.1%). The diagnostic accuracy showed a significant association with the level of experience of the emergency physician involved (P<0.05). CONCLUSION: There should be a higher index of suspicion, better surgical training, and better senior supervision at accident and emergency departments, to avoid preventable morbidity and mortality in acute appendicitis.

A returned traveller with persistent fever due to murine typhus.

Murine (endemic) typhus is a notifiable disease in Hong Kong, but its diagnosis can be difficult. We report a case of murine typhus in a middle-aged man who presented with persistent fever, headache, and skin rash 2 weeks after returning from a visit to China. The diagnosis of murine typhus requires a high index of suspicion for a febrile patient with a history of potential exposure to the disease vector (rat flea) in an endemic area. The importance of early recognition lies in the potential for early therapeutic intervention, leading to decreases in morbidity and duration of stay in hospital.

PCR cloning, heterologous expression, and characterization of isopenicillin N synthase from Streptomyces lipmanii NRRL 3584.

A key step which involves the cyclization of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine to the bicyclic ring structure of isopenicillin N in the penicillin and cephalosporin biosynthetic pathway, is catalyzed by isopenicillin N synthase (IPNS). In this study, an IPNS gene from Streptomyces lipmanii NRRL 3584 (slIPNS) was cloned via PCR-based homology cloning, sequenced and expressed in Escherichia coli. Soluble slIPNS was overexpressed up to 21% of total soluble protein, and verified to be functionally active when in an IPNS enzymatic assay. Sequence comparison of the slIPNS gene obtained (excluding the consensus primer sequences) with another cloned IPNS from S. lipmanii 16884.3, revealed one three-nucleotide deletion and three closely-spaced single nucleotide deletions. Furthermore, this paper also reports the first instance of the usage of PCR as an alternative and rapid strategy for IPNS cloning using consensus primers.

Immunosensitization of prostate carcinoma cell lines for lymphocytes (CTL, TIL, LAK)-mediated apoptosis via the Fas-Fas-ligand pathway of cytotoxicity.

Several reports suggest that immunotherapy mediated by cytotoxic lymphocytes is beneficial in the destruction of drug-resistant tumor cells. Cytotoxic T lymphocytes kill target cells by two main mechanisms, namely by the perforin pathway and by the Fas-ligand (Fas-L) pathway. The role of the Fas-L pathway in tumor cell killing is not clear because many Fas(+)-expressing tumor cells are resistant to the Fas-L agonist cytotoxic anti-Fas antibody. The human prostate tumor cell lines (PC-3, DU145, and LnCAP) express Fas on the cell surface but are resistant to killing by anti-Fas antibody. This study examined the sensitivity of prostate tumor cells to Fas-L-mediated cytotoxicity and sensitization of the tumor cells by drugs to Fas-L-mediated killing. All three prostate tumor cell lines are resistant to Fas-L killing as determined by the use of the murine CTL hybridoma PMMI that kills only through the Fas-L pathway. However, the addition of subtoxic concentrations of CDDP or VP-16 significantly sensitized the PC-3 and DU145, but not LnCAP, tumor cells to Fas-L killing and apoptosis by PMMI. The sensitization of tumor cells by drugs was inhibited by neutralizing anti-Fas antibody. These findings demonstrate that immunoresistant Fas(+)-expressing DU145 and PC-3 prostate tumor cells can be sensitized by drugs to Fas-L killing. We then examined the role of Fas-L killing by TIL and LAK cells. All three prostate tumor cell lines were sensitive to killing by TIL and LAK and cell killing was primarily mediated through the Ca(2+)-dependent perforin pathway because it was blocked by the addition of EGTA/MgCl2. Sensitization by CDDP or VP-16 did not significantly augment killing of untreated tumor cells by TIL or LAK cells. However, in the presence of EGTA/MgCl2, the addition of CDDP or VP-16 significantly augmented killing of PC-3 and DU145, but not LnCAP, by TIL and LAK, and killing was blocked by neutralizing anti-Fas antibody. These findings demonstrate that both TIL and LAK exhibit a Fas-L-mediated killing pathway that is revealed once the perforin pathway is blocked by the Ca2+ chelator EGTA/MgCl2. Altogether, these findings show that drug-resistant, Fas(+)-expressing PC-3 and DU145 prostate tumor cells can be sensitized by CDDP and VP-16 to killing by Fas-L-bearing CTL, TIL, and LAK cells. Sensitization of tumor cells by drugs may augment the efficacy of immunotherapy in the eradication of tumor cells that are resistant to Fas-L-mediated killing.

Beta1PIX, the PAK-interacting exchange factor, requires localization via a coiled-coil region to promote microvillus-like structures and membrane ruffles.

PIX is a Rho-family guanine nucleotide exchange factor that binds PAK. We previously described two isoforms of PIX that differ in their N termini. Here, we report the identification of a new splice variant of betaPIX, designated beta2PIX, that is the dominant species in brain and that lacks the region of approximately 120 residues with predicted coiled-coil structure at the C terminus of beta1PIX. Instead, beta2PIX contains a serine-rich C terminus. To determine whether these splice variants differ in their cellular function, we studied the effect of expressing these proteins in HeLa cells. We found that the coiled-coil region plays a key role in the localization of beta1PIX to the cell periphery and is also responsible for PIX dimerization. Overexpression of beta1, but not beta2PIX, drives formation of membrane ruffles and microvillus-like structures (via activation of Rac1 and Cdc42, respectively), indicating that its function requires localized activation of these GTPases. Thus, beta1PIX, like other RhoGEFs, exerts specific morphological functions that are dependent on its intracellular location and are mediated by its C-terminal dimerization domain.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) for treatment of prostate cancer: first results and review of the literature.

We present the involvement and association of TNF-related apoptosis-inducing ligand (TRAIL) with apoptosis. Its potential application as a therapeutic agent in urologic oncology is discussed. We have examined the sensitivity of prostate carcinoma cell lines DU145, PC3 and LNCaP to TRAIL-induced apoptosis and the expression of TRAIL receptors. Furthermore we looked into the sensitization of those prostate carcinoma cell lines to TRAIL-mediated apoptosis by low toxic levels of actinomycin-D. Furthermore, we review and discuss the pertinent literature on the molecular biology of TRAIL, its receptors and future potential for therapy in urologic oncology. Recent discovery and characterization of TRAIL has led to further broadening and insights into the apoptotic process. Based on preceding in-vitro studies, the first in-vivo study using TRAIL has been conducted and published in 1999. Systemic application of TRAIL in severe combined immune deficient (SCID) mice resulted in tumor regression of subcutaneous implanted mammary and colon cancer and several groups are looking into TRAIL sensitivity of prostate cancer and renal cancer cellines. Our in-vitro data revealed a significant increase of apoptotic cell death rate following the combined application of TRAIL with actinomycin-D. Our results suggest that the combination of TRAIL and ActD may be a therapeutic option in the treatment of drug/hormone refractory prostate carcinoma. In the future TRAIL may be used in combination therapy with other immunotherapies or gene therapies providing a synergistic effect or enhancing the efficacy of chemotherapeutic or radiotherapeutic regimens.

Actinomycin D and gemcitabine synergistically sensitize androgen-independent prostate cancer cells to Apo2L/TRAIL-mediated apoptosis.

The cytotoxic efficacy and kinetics involved in sensitization of Apo2L/TRAIL-resistant, androgen-independent prostate cancer cells to Apo2L/TRAIL or tumor necrosis factor-alpha or Fas ligand-mediated apoptosis were tested using subclinical concentrations of actinomycin D, paclitaxel, cisplatinum, gemcitabine, and radiation in CL-1, LNCaP, DU-145, and PC3 prostate cancer cell lines. CL-1 cells expressed all four Apo2L/TRAIL receptors and were resistant to Apo2L/TRAIL-mediated apoptosis (1-5,000 ng/mL) and to the sensitizers when given alone. Pretreatment with actinomycin D followed by Apo2L/TRAIL or tumor necrosis factor-alpha or anti-Fas CH-11 monoclonal antibody, but not in the reverse order, induced apoptosis in all cell lines. Synergistic sensitization in CL-1 cells was shown also with gemcitabine but not with cisplatinum, VP-16, paclitaxel, or radiation. Incubating the Apo2L/TRAIL-resistant CL-1, LNCaP, DU-145, and PC3 cell lines with 100 ng/mL actinomycin D for 4 hours followed by Apo2L/TRAIL for 24 hours resulted in 45.4 +/- 10.3%, 58.8 +/- 3.6%, 53.4 +/- 1.4%, and 84.2 +/- 8.4% apoptosis, respectively. Prolonging the sensitization time to 24 hours followed by 20 hours of incubation with Apo2L/TRAIL further enhanced the killing activity against CL-1 cells to 89 +/- 1% (delta = 60%, synergistic ratio = 3.1). This killing has a biphasic pattern that was contributed to by apoptosis (83%) and necrosis (17%) at 10 hours (peak) and 40% and 60%, respectively, at 20 hours. These results suggest that prostate cancer cells' resistance to Apo2L/TRAIL-mediated apoptosis can be reversed and synergy is achieved by sensitization of tumor cells with subclinical concentrations of actinomycin D or gemcitabine and may be useful clinically for the treatment of metastatic hormone- and drug-refractory prostate cancer.

Studies of rhodamine-123: effect on rat prostate cancer and human prostate cancer cells in vitro.

The effect of the lipophilic, cationic dye, Rhodamine-123 (Rh-123), on prostate cancer in rats, and on three tumor cell lines in vitro is reported here. The general toxicity of Rh-123 in mice has been found to be minimal. Lobund-Wistar (L-W) rats with the autochthonous prostate cancer of Pollard were treated for six doses with Rh-123 at a dose of 15 mg/kg subcutaneously every other day. Microscopic examination of the tumors revealed cellular and acinar destruction. The effectiveness of Rh-123 as a cytotoxic agent was tested by clonogenic and viability assays in vitro with three human prostate cancer cell lines. Severe (60-95%) growth inhibition was observed following Rh-123 exposure for 2-5 days at doses as low as 1.6 micrograms/ml in all three prostate cancer cell lines.

First case of haemolytic disease of the newborn due to anti-Mur in Hong Kong.

The fifth child of a Hong Kong Chinese mother developed moderate jaundice, attributable to antibodies (anti-Mi) against antigenic determinants in GP.Mur (Miltenberger, class III) red cells. Both the father and the eldest sister were of the phenotype GP.Mur. Testing of maternal serum against a red cell panel including cells known to carry the antigenic determinants of some Miltenberger phenotypes revealed the presence of anti-Mur. This report documents the first case of haemolytic disease of the newborn (HDN) due to anti-Mur in Hong Kong.

Overestimation of the prevalence of antibody to hepatitis C virus in retrospective studies on stored sera.

Serum samples (1,428) from 1,149 patients with chronic liver diseases and polytransfused subjects were tested for antibody to hepatitis C virus by first-generation enzyme immunoassays. Antibody to hepatitis C virus was detected in 87% of patients with transfusion-related chronic non-A, non-B hepatitis; 17.6% of patients with nonmalignant, chronic hepatitis B virus infection; 37.3% of patients with hepatocellular carcinoma; 14.3% of patients with alcoholic liver diseases; 22.2% of patients with cryptogenic cirrhosis; 76% of intravenous drug abusers; 16.4% of patients on hemodialysis; 1.8% of patients on peritoneal dialysis; 6.2% of kidney transplant recipients; and 3.1% of normal subjects. A high frequency of weakly positive results was found in "aged" samples: 61.9% of antibody to hepatitis C virus-positive patients whose sera had been stored for more than 2 yr had optical densities less than two times the cut-off values in contrast to 7.9% of those whose sera had been stored for less than 2 yr (p less than 0.0001). A significantly lower proportion of patients who had optical densities less than two times the cut-off values were reactive in subsequent samples, 27.5% vs. 87.5% (p less than 0.0001). On retests, only 70% and 56% of sera that were initially positive for antibody to hepatitis C virus remained antibody to hepatitis C virus positive using second-generation enzyme immunoassays and neutralization enzyme immunoassays, respectively. Our results suggest that retrospective studies on stored sera may have overestimated the prevalence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

A controlled trial of interferon with or without prednisone priming for chronic hepatitis B.

In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels.