Characterization of reaerosolization from impingers in an effort to improve airborne virus sampling.

AIMS: To assess the impact of reaerosolization from liquid impingement methods on airborne virus sampling. METHODS AND RESULTS: An AGI-30 impinger containing particles [MS2 bacteriophage or 30-nm polystyrene latex (PSL)] of known concentration was operated with sterile air. Reaerosolized particles as a function of sampling flow rate and particle concentration in the impinger collection liquid were characterized using a scanning mobility particle sizer. Reaerosolization from the impinger was also compared to that from a BioSampler. Results show that reaerosolization increases as flow rate increases. While the increased particle concentration in the impinger collection liquid leads to an increase in the reaerosolization of PSL particles, it does not necessarily lead to an increase in the reaerosolization of virus particles. Reaerosolization of virus particles begins to decrease as the particle concentration in the impinger collection liquid rises above 10(6) PFU ml(-1). This phenomenon results from aggregation of viral particles at high concentrations. Compared with micron-sized particles, nanosized virus particles are easier to aerosolize because of reduced inertia. Reaerosolization from the BioSampler is demonstrated to be significantly less than that from the impinger. CONCLUSIONS: Reaerosolization from impingement sampling methods is a mode of loss in airborne virus sampling, although it is not as significant a limitation as the primary particle size of the aerosol. Utilizing a BioSampler coupled with short sampling periods to prevent high accumulative concentrations can minimize the impact of reaerosolization. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms reaerosolization of virus particles to be a mode of loss in impingement sampling and identifies methods to minimize the loss.

Parallel propagating electromagnetic waves in magnetized quantum electron plasmas with finite temperature.

We studied parallel propagating electromagnetic waves in a magnetized quantum electron plasma of finite temperature, as an extension of our previous study on a zero temperature plasma. We obtained simple analytic dispersion relations in the long wavelength limit that included the thermal effect as correction terms to the zero temperature results. As in the zero temperature case, the lower branch of the R wave showed significant damping and became ill-defined at short wavelengths. Quantum effects seemed to give qualitative changes, such as the appearance of anomalous dispersion regions, to the classical dispersion relations when v_{F}/v_{th}≤0.2 for a set of exemplary parameters of v_{F}=0.1c and ω_{ce}/ω_{pe}=0.05 was used. We also noted that introduction of the Planck constant in the quantum Vlasov equation changed the shape of the anomalous dispersion region qualitatively, by forming a normal dispersion region in the middle of the original single broad anomalous dispersion region.

Cerebrospinal fluid asparagine concentrations after Escherichia coli asparaginase in children with acute lymphoblastic leukemia.

PURPOSE: The CNS is an important sanctuary site in childhood acute lymphoblastic leukemia (ALL). CSF asparagine concentration reflects asparaginase systemic pharmacodynamics. We evaluated the time course of CSF asparagine depletion in children with ALL during and after a course of Escherichia coli asparaginase. PATIENTS AND METHODS: Thirty-one children (24 newly diagnosed and seven at relapse) received E coli asparaginase 10,000 IU/m2 intramuscularly three times weekly for six and nine doses, respectively, as part of multiagent induction chemotherapy. CSF asparagine levels were measured before, during, and after asparaginase dosing. RESULTS: The percentage of patients with undetectable (< 0.04 micromol/L) CSF asparagine was 3.2% (one of 31 patients) at baseline, 73.9% (17 of 23) during asparaginase therapy, and 56.3% (nine of 16) 1 to 5 days, 43.8% (seven of 16) 6 to 10 days, 20.0% (two of 10) 11 to 30 days and 0% (zero of 21) more than 30 days after asparaginase therapy. The proportion of patients with depleted CSF asparagine was higher during asparaginase therapy than at baseline (P < .001), 11 to 30 days (P = .003), and more than 30 days after asparaginase therapy (P < .001). Median CSF asparagine concentrations were 4.42 micromol/L before, less than 0.04 micromol/L during, and less than 0.04 micromol/L at 1 to 5 days, 1.63 micromol/L at 6 to 10 days, 1.70 micromol/L at 11 to 30 days, and 5.70 micromol/L at more than 30 days after asparaginase therapy, respectively. CSF depletion was more common in patients with low baseline CSF asparagine concentrations (P = .003). CONCLUSION: CSF asparagine concentrations are depleted by conventional doses of E coli asparaginase in the majority of patients, but they rebound once asparaginase therapy is completed.

Hypersensitivity or development of antibodies to asparaginase does not impact treatment outcome of childhood acute lymphoblastic leukemia.

PURPOSE: Development of antibodies and hypersensitivity to asparaginase are common and may attenuate asparaginase effect. Our aim was to determine the relationship between antiasparaginase antibodies or hypersensitivity reactions and event-free survival (EFS). PATIENTS AND METHODS: One hundred fifty-four children with acute lymphoblastic leukemia received Escherichia coli asparaginase 10,000 IU/m(2) intramuscularly three times weekly for nine doses during multiagent induction and reinduction phases and for seven monthly doses during continuation treatment. Erwinia asparaginase was used in case of clinical hypersensitivity to E coli but not for subclinical development of antibodies. Plasma antiasparaginase antibody concentrations were measured on day 29 of induction in 152 patients. RESULTS: Antibodies were detectable in 54 patients (35.5%), of whom 30 (55.6%) exhibited hypersensitivity to asparaginase. Of the 98 patients who had no detectable antibodies, 18 (18.4%) had allergic reactions. Patients with antibodies were more likely to have a reaction than those without antibodies (P <.001). Among the 50 patients who experienced allergic reactions (including two for whom antibodies were not measured), 36 (72.0%) were subsequently given Erwinia asparaginase; seven (19.4%) reacted to this preparation. EFS did not differ among patients who did and did not have antibodies (P =.54), with 4-year EFS (+/- 1 SE) of 83% +/- 6% and 76% +/- 5%, respectively. Similarly, EFS did not differ among patients who did and did not develop allergic reactions (P =.68), with 4-year estimates of 82% +/- 6% and 78% +/- 5%, respectively. CONCLUSION: In this setting, in which most patients with allergy were switched to another preparation, there was no adverse prognostic impact of clinical or subclinical allergy to asparaginase.

Anti-asparaginase antibodies following E. coli asparaginase therapy in pediatric acute lymphoblastic leukemia.

Asparaginase is an effective antileukemic agent and is included in most front-line protocols for pediatric acute lymphoblastic leukemia (ALL) worldwide; however, allergic reactions to asparaginase may be dose-limiting. We evaluated plasma anti-asparaginase antibody concentrations in a cohort of children with newly diagnosed ALL, who did and who did not exhibit clinical hypersensitivity, after Escherichia coli (E. coli) asparaginase therapy. Thirty-five children who received asparaginase 10000 IU/m2 i.m. three times weekly for nine doses as part of both multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Twenty-two patients experienced initial allergic reactions to asparaginase during continuation (n=20) or reinduction (n=2) phases and 13 children did not exhibit any reaction. An enzyme-linked immunosorbent assay (ELISA) was used to measure anti-asparaginase antibodies in plasma samples, diluted 1:3200, using E. coli asparaginase as the antigen. The median anti-asparaginase antibody concentration (OD at 1:3200 dilution) increased from 0.039 at induction to 0.506 at reinduction in patients who exhibited clinical hypersensitivity (P = 0.0002). By comparison, median antibody level increased from 0.011 to 0.032 OD at identical time points in patients who did not react to asparaginase (P = 0.02). Both post-induction and post-reinduction anti-asparaginase antibody levels were higher in reacting than in nonreacting patients (P = 0.004 and P = 0.01, respectively). Antibody levels were inversely related to the time elapsed between the reaction and sampling (P = 0.011). Although anti-asparaginase antibody levels increased from the post-induction plasma sample to the post-reinduction sample in 28 of 35 patients regardless of whether they exhibited clinical hypersensitivity, patients with hypersensitivity reactions had higher antibody levels than did identically treated control patients at comparable time points in therapy. Therefore, antibody analysis may be of clinical value in predicting future hypersensitivity.

Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients.

To evaluate how well antibodies to one asparaginase preparation predict or correlate with antibodies to another preparation in acute lymphoblastic leukemia (ALL) and lymphoma patients who did and did not have hypersensitivity reactions during chemotherapy. In all, 24 children with newly diagnosed ALL or lymphoma, who received Escherichia coli asparaginase 10 000 IU/m(2) IM thrice weekly for nine doses as part of multiagent induction and reinduction chemotherapy, and seven monthly doses during the first 7 months of continuation treatment, were studied. Plasma samples were collected at postinduction and at postreinduction. Six of 24 patients had no overt clinical reactions (nonreacting) and received only the E. coli preparation. Of these, 18 patients who had allergic reactions were switched to Erwinia asparaginase. A total of 18 patients had an anaphylactoid reaction to Erwinia asparaginase and were switched to receive polyethylene glycol (PEG) asparaginase. Antibody levels were measured by enzyme-linked immunoadsorbent assay against all the three asparaginase preparations. At postinduction, antibodies against E. coli were higher in reacting patients (0.063+/-0.066) than in nonreacting patients (0.019+/-0.013) (P=0.03). At postreinduction, anti-Erwinia antibodies were significantly higher in reacting patients (0.431+/-0.727) than in nonreacting patients (0.018+/-0.009) (P=0.007). Anti-E. coli antibodies correlated with anti-PEG antibodies at postinduction (r=0.714, P<0.001) and at postreinduction (r=0.914, P<0.001), but did not correlate with anti-Erwinia antibodies at postinduction (r=0.119, P=0.580) and at postreinduction (r=0.078, P=0.716). The results indicate a crossreactivity between patient antibodies raised against natural E. coli and PEG asparaginase but not Erwinia asparaginase.

Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies.

Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild-type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies.

Phase I targeted systemic exposure study of paclitaxel in children with refractory acute leukemias.

Clearance of anticancer drugs in children is highly variable, leading to wide variability in the systemic exposure associated with each dosage escalation in Phase I studies. The purpose of this Phase I study was to escalate targeted systemic exposure to paclitaxel, rather than dose, to attenuate the impact of pharmacokinetic variability at each escalation level. Children with recurrent acute leukemias received paclitaxel as 24-h infusions at escalating levels of paclitaxel systemic exposure [i.e., area under the concentration-versus-time curve (AUC)]. Plasma paclitaxel concentrations were measured by high-performance liquid chromatography-UV detection. A Bayesian algorithm using a two-compartment model with saturable distribution and saturable elimination was used to estimate clearance during the first 8 h of infusion; the infusion rate was adjusted 12 h after the start of infusion to achieve the target AUC. Toxicity and evidence of activity were assessed after each course. Six boys and one girl received eight courses of paclitaxel. The target AUC ranged from 31.5 to 45 microM x h. Five of the seven evaluable courses had AUCs between 75% and 125% of the target after adjustment (median, 100.2%; range, 51-151%), whereas none of the seven courses was projected to be in the target range had no change in dose been made (P = 0.021). The ratio of the achieved AUC to the target AUC was inversely related to clearance (r = -0.857; P = 0.014). Mucositis was the exposure-limiting toxicity, at AUCs lower than were expected based on Phase I studies in children with solid tumors. Pharmacokinetically-guided dosing strategies reduced variability in systemic exposure. Alternatives to traditional Phase I studies may be important in the setting of childhood leukemias because these patients show poor tolerance to Phase I therapy.

ELISA to evaluate plasma anti-asparaginase IgG concentrations in patients with acute lymphoblastic leukemia.

The development of antibodies to asparaginase may attenuate the pharmacologic effect of asparaginase treatment, may be associated with hypersensitivity reactions, and may necessitate switching to a different commercial asparaginase preparation for current or future therapy. Thus, development of an ELISA for measurement of anti-asparaginase antibody levels is important in the clinical setting. An anti-asparaginase antibody reference was established by screening 65 plasma samples from six patients with acute lymphoblastic leukemia (ALL) who had recently developed a hypersensitivity reaction to Escherichia coli or Erwinia chrysanthemi asparaginase therapy. Twenty-one plasma samples were selected for the anti-asparaginase antibody reference pool. Five micrograms per milliliter of commercial E. coli and Erwinia asparaginase and 10 microg/ml of E. coli asparaginase conjugated with polyethylene glycol (PEG asparaginase) were found to be optimal as coating antigen concentrations. Anti-asparaginase antibody concentrations were determined using a commercial polyclonal goat anti-human IgG horseradish peroxidase conjugate. The antibody reference curves were linear in a range of absorbance from 0.1 to 1. 5 O.D. units for dilutions from 1:1600 to 1:51,200. Inter-assay coefficients of variation were 9.04, 14.7 and 13.0%, and intra-assay coefficients of variation were 1.44, 4.43 and 3.28% for antibodies against E. coli, Erwinia, and PEG L-asparaginase, respectively. The cut-off for positivity in plasma was determined as mean+2 S.D. of the optical density values for plasma from untreated healthy volunteers. Measurement of specific IgG by this ELISA allows for the evaluation of plasma anti-asparaginase antibody concentrations in patients receiving one or more of the multiple commercial L-asparaginase preparations.

Headache, circumoral paresthesia, and facial flushing associated with high-dose carmustine infusion.

We describe seven patients who developed symptoms including severe headache, circumoral paresthesia, and facial flushing during high-dose carmustine (BCNU) infusion as part of the preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation for metastatic breast cancer. Five patients responded to pain medications, including partial and complete opiate receptor agonists. Premedication of subsequent doses of BCNU with corticosteroids, pain medications, or benzodiazepines lessened, but did not prevent the same symptoms from recurring. The incidence and mechanism of this toxicity are unknown, but this adverse syndrome should be considered when administering high-dose BCNU infusions.

Pharmacokinetics of paclitaxel in an anephric patient.

PURPOSE: To assess the pharmacokinetics of paclitaxel for recurrent Wilms' tumor in an anephric pediatric patient receiving hemodialysis. METHODS: Paclitaxel was administered at a dose of 250 mg/m2 and 350 mg/m2 by 24-h continuous intravenous (IV) infusion as two consecutive courses, respectively, separated by approximately 3 weeks. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: Paclitaxel disposition was comparable to that reported in similarly treated children with normal renal function. For the first course (250 mg/ m2), paclitaxel concentrations were best fit by a two-compartment, first-order model. The calculated pharmacokinetic parameters were 0.312 h(-1) for the first-order rate constant of elimination (Ke), 52.4 l/m2 for the apparent volume of distribution (Vc), 0.170 h(-1) and 0.105 h(-1) for the first-order rate constants for transit from central to peripheral compartments (Kcp) and peripheral to central compartments (Kpc), respectively, 16.9 microM x h for the area under the plasma concentration-versus-time curve (AUC), and 273 ml/min per m2 for average clearance (Cl). The concentration-versus-time data with the second course (at the higher dosage of 350 mg/m2) were better described by a two-compartment model with saturable elimination. The calculated pharmacokinetic parameters were 12.0 micromol x h(-1) for the maximal rate of elimination (Vm1-0), 0.158 microM for the concentration at which the rate of elimination is 50% of maximal (Km1-0), 0.809 h(-1) for Kcp, 0.0792 h(-1) for Kpc, 23.5 l/m2 for Vc, 20.9 microM x h for AUC, and 327 ml/min per m2 for Cl. Paclitaxel was undetectable in the dialysate. CONCLUSIONS: The level of systemic exposure in our anephric patient was comparable to or lower than that achieved in patients with normal renal function at similar dosages. The patient tolerated therapy without problems. It appears that pediatric patients in renal failure can be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.

Asitrilobins A and B: cytotoxic mono-THF annonaceous acetogenins from the seeds of Asimina triloba.

The seeds of Asimina triloba have yielded two novel cytotoxic mono-tetrahydrofuran (THF) Annonaceous acetogenins, asitrilobins A (1) and B (2). In addition, annonacin, asimin and asiminacin, which are known, and annomontacin and xylomaticin, which are known but are new in this species, were obtained. Compounds 1 and 2 have a relative stereochemical relationship of erythro/cis/threo across the mono-THF ring with its two flanking hydroxyls and they, thus, represent a new type of acetogenin. Their structures were established on the basis of chemical and spectral evidence. 1 and 2 showed potent bioactivities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (MIA PaCa-2) at ten to one-hundred times the potency of adriamycin.

A review of the effects of plasmapheresis on drug clearance.

Plasmapheresis (PP) is being increasingly performed to treat a number of infectious, immunologic, metabolic, and inherited illnesses. In this procedure, plasma and cellular components of blood are separated, and all solutes in plasma, including drugs, can be removed. The effects of PP on the pharmacokinetics of drugs administered therapeutically and taken in overdose are evolving. As the procedure becomes more widely performed, it is important that these effects be understood.

A human lymphoid leukemia cell line with a V(D)J recombinase-mediated deletion of hprt.

Large deletions of exons 2 and 3 of the hprt gene are the most common type of hprt mutation in lymphocytes of newborn infants, and their frequency increases in cultured human T-lymphoid cells as a result of exposure to etoposide. Sequenced PCR products for these deletions are consistent with a V(D)J recombinase-mediated mechanism underlying their genesis. Herein, we describe the isolation and characterization of an etoposide-induced mutant CEM cell line that is clonal for a V(D)J recombinase-mediated exon 2 + 3 deletion. Human CCRF-CEM cells were exposed to 5 muM etoposide for 4 h, selected in 6-thioguanine, and an exon 2 + 3 deletion mutant was isolated through serial limiting dilution, using a PCR-based assay for detection of the exon 2 + 3 deletion. Untreated CEM cells and cells treated with 6-thioguanine alone were similarly subcultured. The exon 2 + 3 deletion-containing line was termed SJCEM808 and had a slightly longer doubling time than the control lines, tended to clump in suspension, and was characterized by cell membrane blebbing. Compared to the parent line, SJCEM808 had similar cytogenetic abnormalities, lower CD2, CD1, and CD10 expression, and negligible RAG-1 expression. However, RAG-1 expression was down-regulated in some untreated parental subclones following similar subculturing. The sequence of the exon 2 + 3 deletion mutation exhibited nucleotide insertions, and the breakpoints were adjacent to heptamer signal recognition sequences in intact hprt, consistent with a V(D)J recombinase-mediated mechanism underlying its genesis. There were no MLL gene or interlocus T-cell receptor (TCR) rearrangements. These results indicate that non-homologous recombination following etoposide treatment is neither necessarily accompanied by other large DNA rearrangements nor simply a pre-lethal event, and this cell line may serve as a useful tool for studying illegitimate V(D)J recombinase-mediated deletions.

Annomocherin, annonacin and annomontacin: a novel and two known bioactive mono-tetrahydrofuran annonaceous acetogenins from Annona cherimolia seeds.

A novel and two known bioactive mono-tetrahydrofuran (THF) annonaceous acetogenins, annomocherin (1), annonacin (2) and annomontacin (3), have been isolated from the fractionated ethanolic extracts of the seeds of Annona cherimolia, guided by the brine shrimp lethality test (BST). Their structures were elucidated on the basis of spectroscopic and chemical methods. All compounds have a relative stereochemistry of threo/trans/threo for the mono-THF ring with two flanking hydroxyls. Compound 1 has a double bond at C-23/24 of aliphatic chain. Compound 1 was isolated from natural sources for the first time, and was named annomocherin. Two known Compounds 2 and 3 which have never been isolated from this species before, were obtained. Compound 1 exhibited potent and selective cytotoxicities against the breast carcinoma (MCF-7) and kidney carcinoma (A-498) cell lines with 100 to 1,000 times the potency of adriamycin. In brine shrimp lethality test (BST), 1-3 exhibited cytotoxicity.

cis-Annonacin and (2,4)-cis-and trans-isoannonacins: cytotoxic monotetrahydrofuran annonaceous acetogenins from the seeds of Annona cherimolia.

cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated from the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3).

Association of SIADH with selective serotonin reuptake inhibitors.

While SSRIs have been reported to cause SIADH, the actual incidence remains unclear. From the published case reports, the elderly may appear to be at higher risk of developing SIADH. Symptomatic and laboratory presentation in these patients includes lethargy, hyponatremia, elevated urinary sodium excretion, and hyperosmolar urine. However, evaluation of SSRI-induced SIADH has been incomplete. Normalization of serum sodium concentrations occurred after discontinuation of the SSRI and/or fluid restriction. Of the published reports, only three convincingly demonstrated a causative role of SSRI-induced SIADH by rechallenge. As a result, the published case reports cannot definitely established a causal relationship. Pharmacists can play an important role in the care of patients with suspected SSRI-induced SIADH. Pharmacists should be familiar with the clinical and biochemical presentation of SIADH as well as the limitations of published case reports implicating SSRIs as a cause of SIADH. A complete medication history, including when these agents were initiated or discontinued, should be taken. Pharmacists must understand, recognize, and ensure the proper monitoring parameters, namely daily fluid intake, patient weight, and serum sodium concentrations.

Interferon alfa in the treatment of chronic viral hepatitis B and C.

OBJECTIVE: To review the indications, efficacy, and toxicity of interferon alfa in the treatment of chronic hepatitis B and C. DATA SOURCES: English-language literature pertaining to chronic hepatitis B and C and their management with interferon reported between 1980 and June 1995 was identified through computer searches using MEDLINE and through extensive searching of bibliographies and identified articles. DATA SYNTHESIS: Two major causes of chronic hepatitis are hepatitis B virus and hepatitis C virus (HBV and HCV). Worldwide, HBV infection is a major cause of cirrhosis and hepatocellular carcinoma, but in the US it is mainly a disease of high-risk groups. In the US, and particularly the southern portion, HCV is more common. Like HBV, HCV also may cause cirrhosis and hepatocellular carcinoma. Except for interferon therapy, the ability to effectively treat chronic hepatitis is limited. Interferon has antiviral, antiproliferative, and immunomodulatory activity. This agent is indicated in patients who have histologic evidence of chronic hepatitis and ongoing viral replication. Thirty percent to 40% of patients with HBV achieve loss of serum HBV e antigen and HBV DNA after treatment with interferon alfa 5 million units/d or 10 million units three times weekly for 16 weeks. Fifty percent of patients with chronic HCV respond to interferon 3 million units three times weekly for 6 months, but half of these relapse within the next 6 months. Prolonged use (18 months) may provide longer term responses in HCV. Adverse effects are common, often dose-dependent, and usually transient. A flu-like syndrome occurs early in the treatment, but fatigue is the most common adverse effect and persists throughout therapy. Long-term interferon treatment has not been extensively evaluated and the impact on survival rates is not known. CONCLUSIONS: Interferon is the only agent to have shown a consistent therapeutic effect on chronic hepatitis. Response of HBV to interferon is usually sustained, while a recurrence of HCV occurs in 50% of those who initially respond. Despite the benefits of interferon, its adverse effects and impact on hepatitis must be considered before treatment can be freely advocated.

[The effect of various cleansing methods for total fiber optic colonoscopy].

It is a fact that there are recent increasing trends of incidence of the colorectal carcinoma among other colorectal diseases. In such trend, the early detection remain to be most important by the air contrast barium enema and total fiber optic colonoscopy There are several ways to prepare the colon for barium enema and fiber optic colonoscopy which include several agents. The mechanical cleansing have been used most frequently since Brown's method was adapted to be most perfect for colon cleansing. The ideal laxatives and enema solutions were limited to adequate dose, it's effectiveness, patient's diet and bowel habit, minimal side effect, low cost and simple to perform. In order to compare the effectiveness of various cleansing solutions, six experimental methods were formed as shown; 1. normal saline enema, 2. castor oil with normal saline enema, 3. castor oil with soapsuds enema, 4. magnesium citrate with normal saline, 5. magnesium citrate with soapsuds enema and 6. ingestion of Golyetly solution. The authors have compared and determined the degree of cleanliness by an experienced endoscopist The total number of patients was 247, age distribution was 43 +/- 15 years old, and sex distribution was 133 males and 114 females. The grade I and II represented no difficulties at performing the fiber optic colonoscopy+, but grade III and IV had some difficulties, even unable to perform the fiber optic colonoscopy. The effectiveness the cleansing agents, represented with grade I and II was 95.9% (47/49) in method 6, 93.2% (54/58) in method 2, 83.3% (30/33) in method 3, 70.0% (28/40) in method 5, 66.7% (16/24) in method 1, and 45.7% (18/40) in method 4. Method 2 and 6 were the most effective in normal bowel habit patients. In constipated patients, method 6 was the most effective and all method except method 4 were effective in diarrhea patients. The degrees of less mucosal irritation by various bowel cleansing method were in the order of method 6(100%), 1(100%), 5(74%), 2(69%). In subjective symptoms and cleansing groups, abdominal distension, pain, nausea and vomiting were complained, and that's subject symptoms were in the order of method 3(88.9%), 6(79.6%), 1(75%), 5(72.5%), 2(72.4%), 4(67.5%). In conclusion, we believe that the Golytely of the mechanical cleansing solution for fiber optic colonoscopy was the most effective, but others depended on the patient's condition and bowel habit.