Feasibility of video observed therapy to support controller inhaler use among children in West Baltimore.

OBJECTIVE: To assess feasibility of a novel video directly observed therapy (DOT)-based digital asthma program intended to support correct inhaled corticosteroid (ICS) use among children. METHODS: We conducted a 60-day pilot study among patients 2-18 years attending a primary care clinic with prescribed ICS and sub-optimally controlled asthma (recent hospitalization, ICS nonadherence, frequent rescue inhaler use, therapy escalation, or Asthma Control Test <20). Participants used a mobile application to receive reminders, submit videos of ICS doses (video DOT), and receive asynchronous feedback on adherence and inhaler technique. We assessed enrollment, engagement, program metrics, and user experience; adherence and inhaler errors were secondary outcomes. RESULTS: Of 26 eligible patients, 21 (81%) enrolled and submitted ≥1 video; median age was 11 years (8-15), 71% were male, 90% had Medicaid, and 62% experienced ≥1 exacerbation in the previous 6 months. Retention was 57% and 52% at week 5 and 8, respectively. Participants submitted 810 videos. Missed doses, inhaler errors (n = 247) and adherence issues (n = 107) prompted 543 communications; inadequate inspiration or holding breath were most common. Among 16 patients with engagement >7 days and >4 videos, median inhaler error rate (proportion of videos with ≥1 error) decreased from week 1 to week 2 (73% vs 8%, p ≤ 0.05) with median adherence >80%. Participants experienced the program as long, but easy to use; benefits included building routines, skill, and independence. CONCLUSIONS: This pilot study suggests high program acceptability among our cohort. High engagement with improved inhaler technique over the first 14 days suggests shorter implementation.Supplemental data for this article is available online at at.

Impact of maternal hepatitis B virus coinfection on mother-to-child transmission of HIV.

OBJECTIVES: Despite high hepatitis B virus (HBV) endemicity in various resource-limited settings (RLSs), the impact of maternal HIV/HBV coinfection on infant health outcomes has not been defined. We aimed to assess the prevalence of HBV coinfection among HIV-infected pregnant women and its impact on HIV transmission and infant mortality. METHODS: In this study, the seroprevalence of HBV coinfection was determined among HIV-infected pregnant women enrolled in the Six-Week Extended-Dose Nevirapine (SWEN) India trial. The impact of maternal HIV/HBV coinfection on mother-to-child transmission (MTCT) of HIV and infant mortality was assessed using univariate and multivariate logistic regression analysis. RESULTS: Among 689 HIV-infected pregnant Indian women, 32 (4.6%) had HBV coinfection [95% confidence interval (CI) 3.4%, 5.3%]. HBV DNA was detectable in 18 (64%) of 28 HIV/HBV-coinfected women; the median HBV viral load was 155 copies/mL [interquartile range (IQR) < 51-6741 copies/mL]. Maternal HIV/HBV coinfection did not increase HIV transmission risk [adjusted odds ratio (aOR) 1.06; 95% CI 0.30, 3.66; P = 0.93]. Increased odds of all-cause infant mortality was noted (aOR 3.12; 95% CI 0.67, 14.57; P = 0.15), but was not statistically significant. CONCLUSIONS: The prevalence of active maternal HBV coinfection in HIV-infected pregnant women in India was 4.6%. HIV/HBV coinfection was not independently associated with HIV transmission.

Detrimental effects of a failed infection by a co-invasive parasite on a native congeneric parasite and its native host.

Biological invaders often are accompanied by co-invasive parasites that can alter ecosystem function and established native host-parasite relationships. When these co-invasive parasites establish in a community, they can affect native host fitness and native parasite infection intensity, prevalence, and success within the native host. The mosquito, Aedes triseriatus, is North American host to protozoan parasite, Ascogregarina barretti. In geographic regions invaded by the mosquito Aedes albopictus, A. triseriatus may also be infected by A. albopictus' co-invasive parasite, Ascogregarina taiwanensis. We tested the hypotheses that: 1) The presence of a co-invasive parasite will negatively affect native parasite fitness, yielding decreased infection intensity, prevalence, and infection success, which could be caused by immune induction of the host or inter-parasite competition, and 2) Coinfection with the native and co-invasive parasites will negatively affect host fitness, yielding increased larval development time and decreased survival and reproductive fitness, caused by increased costs of infection. In our coinfection experiments we find that any exposure to the co-invasive parasite resulted in decreased survivorship and increased development time of the host A. triseriatus, with or without coinfection by the native parasite. Exposure to both co-invasive and native parasites yielded reduced native parasite infection intensity in the host larva and reduced native parasite propagule production in the resulting male adults. Together, these results indicate not only the potential for the co-invasive parasite to alter the native host-parasite relationship, but to impact native host population dynamics.

Immunoglobulin and other surface antigens of cells of the immune system.

Immunoglobulins (Ig) on cells of the immune system: The cytotoxicity test, with class-specific and type-specific anti-Ig sera, identifies kappa and micro determinants on mouse lymphocytes. The proportion of kappa(+) cells is characteristic for each source of cells: 30% of bone marrow cells, 40% of cells from peripheral lymph nodes, 45% of lymphocytes from peripheral blood or peritoneal cavity, and 50% of spleen cells. No Ig was demonstrable on thymocytes or on leukemia cells (most of which arise from thymus-derived [T] cells). Cytotoxicity tests were performed on various myelomas secreting different Ig; the only positive reactions were given by kappagamma1 myelomas (all four kappagamma1 myelomas tested were sensitive to both anti-kappa and anti-gamma1). Hemolytic plaque-forming cells (PFC) of IgG type had no demonstrable surface Ig, but a proportion of IgM PFC were kappa(+)micro(+). Virtually all rosette-forming cells (RFC) have surface Ig, more than 90% of them being inhibited by anti-kappa, 50% by anti-micro, and 10-30% by antisera to other heavy chains. Anti-lambda sera gave no positive reactions with any cell type, which is in keeping with the low level of this light chain in mouse serum. Ig and other differentiation antigens as markers for T and B cells: Thymocytes are hallmarked by the alloantigens TL, theta, and the Ly series, and it is generally held that extrathymic lymphoid cells that bear them are derived from thymocytes. There is one alloantigen marker for the thymus-independent (B) cell, and that is PC, which appears late in differentiation. (The mouse-specific lymphocyte (MSLA) and mouse-specific bone marrow-derived lymphocyte (MBLA) antigens recognized by heteroantisera, not used in the present study, are other candidates for T and B cell markers.) Making use of antisera to these surface antigens to inhibit the function of cells that carry them, we find the following: Approximately 30% of RFC, 60% of IgM PFC, and 90% of IgG are PC(+) and so are identified as B cells. No T markers were demonstrable on these cell populations. Thus if T cells do become RFC or PFC they presumably lose their T surface markers in the process (cf. the quantitative reduction of T markers accompanying the thymocyte --> lymphocyte transition). Cells that have the potential to initiate graft-versus-host (GVH) reactions have the T cell surface phenotype theta(+)Ig(-). Adoptive transfer of thymus-dependent antibody-forming capacity (response to sheep erythrocytes) required theta(+) cells but transfer of a thymus-independent immune response to Brucella antigen did not. Cells with surface Ig were involved in both types of adoptive transfers. Thus the presently available T markers do not provide evidence for T cells carrying surface Ig. Suppression of the Ig phenotype by antibody: antigenic modulation? A phenotypic change from Ig(+) to Ig(-) occurs when Ig(+) lymphocytes or myeloma cells are incubated with anti-Ig sera in vitro in the absence of complement (C). As with antigenic modulation in the TL system, which it resembles, this phenomenon is temperature dependent and in the case of lymph node cells (LNC) can be inhibited by high doses of actinomycin D.

Bilateral subthalamic stimulation improves gait initiation in patients with Parkinson's disease.

Impaired gait initiation is one of the typical sign of advanced Parkinson's disease (PD). This is the first study to examine quantitatively the effect of deep brain stimulation of the subthalamic nucleus on the performance of gait initiation for patients with advanced PD. A total of 11 patients after surgery of bilateral deep brain stimulation of the subthalamic nucleus (STN) were tested in both the deep brain stimulation (DBS) ON and OFF conditions and/or in both the medication ON (i.e., with the usual dosage of antiparkinsonian medications administered) and OFF (i.e., with the usual dosage of antiparkinsonian medications withheld) conditions. DBS had no effect on the onset of anticipatory postural adjustment (APA). The effect of DBS approached significant level for the onset of swing foot lifting, but reached significant level for the delay of swing foot lifting. DBS significantly increased the amplitude of the APA, amplitude of reactive shear forces on both feet, and amplitude of COP in both anterior-posterior and medial-lateral directions. It is concluded that DBS significantly improved the performance of patients with advanced PD in gait initiation.

In vitro alpha-fetoprotein synthesis by monkey hepatocellular carcinoma.

Five monkeys were treated ip with N-nitrosodiethylamine (DENA), and one was treated with 1-nitrosopiperidine (PIP), starting within 2 months of birth, until hepatocellular carcinoma (HCC) developed. All animals except the PIP-treated monkey had much elevated serum alpha-fetoprotein (AFP) values. Fresh, minced, biopsy-derived tumor was cultured with L-[14C]leucine and L-[14C]lysine. Synthesis of AFP was determined by radioimmunoassay and by specifically precipitable [14C]AFP. Good agreement between these two parameters was obtained for the 4 DENA-induced tumors synthesizing AFP in culture. Tumor from 1 DENA-treated monkey did not synthesize AFP. In addition, neither normal liver nor tumor from the PIP-treated monkey showed AFP synthesis. Rates of synthesis were 0.37-5.50 ng AFP/mg tumor/day, or 0.0012-0.0183 pg AFP/cell/day (if one assumes 3.0 X 10(5) cells/mg tissue) over 48 or 72 hours. Different nodules from the same animal had similar rates of synthesis. For tumors that synthesized AFP in culture, a positive correlation was generally found between rate of synthesis and serum AFP level. The rate of in vitro AFP synthesis observed was lower than that of immunoglobulin synthesis in human myeloma or of AFP synthesis in a rat HCC, but it was close to the estimated rate of AFP synthesis in a monkey HCC line in long-term culture.

Carcinogenicity of aflatoxin B1 in rhesus monkeys: two additional cases of primary liver cancer.

Three of 42 (7%) monkeys given aflatoxin B1 (AFB1) for longer than 2 years have developed primary malignant neoplasms of the liver. Liver biopsies performed at intervals during aflatoxin administration revealed that neoplasia was preceded by pathologic lesions of the liver, including toxic hepatitis, proliferation of pseudotubules, and hyperplastic nodules. Serum alpha-fetoprotein levels, monitored in one of the monkeys by radioimmunoassay, paralleled tumor growth and recurrence of the hepatocellular carcinoma. Normal serum alpha-fetoprotein levels were noted for a monkey with hemangioendothelial sarcoma. Our results implicate AFB1 as a liver carcinogen in monkeys and add additional support to the hypothesis that humans exposed to this substance may be at risk of developing liver cancer.

Carcinogenicity and hepatotoxicity of cycasin and its aglycone methylazoxymethanol acetate in nonhuman primates.

The carcinogenic potential of cycasin and methylazoxymethanol (MAM) acetate was investigated in nonhuman primates. Old-world monkeys (rhesus, cynomolgus, and African green monkeys) received cycasin and/or MAM acetate by oral or ip routes up to 11 years. Eighteen monkeys survived longer than 2 months after initiation of treatment with cycasin (50-75 mg/kg) or MAM acetate (1.5-3.0 mg/kg) given orally 5 days/week; 9 of the animals were necropsied. Histopathologic examination of a liver tumor from 1 of these monkeys revealed well-differentiated hepatocellular carcinoma. A second monkey had multiple tumors, including hepatocellular carcinoma, intrahepatic bile duct adenocarcinoma, renal carcinoma and adenomas, and adenomatous polyps of the colon. Although liver tumors were not observed in the other monkeys, all but 1 monkey had hepatic lesions such as toxic hepatitis and cirrhosis. These monkeys had received cycasin and/or MAM acetate for an average of 57 months (range, 2-133 mo). A group of 10 monkeys received MAM acetate by weekly ip injections (3-10 mg/kg). Six of these animals developed tumors after receiving an average of 6.14 g (range, 3.58-9.66 g) of MAM acetate for an average of 75 months (range, 50-89 mo). Four of the monkeys developed hepatocellular carcinomas, and 2 had multiple primary tumors including hepatocellular carcinomas, renal carcinomas, squamous cell carcinomas of the esophagus, and adenocarcinomas of the small intestine. Our results showed that long-term administration of cycasin and/or MAM acetate by oral and ip routes was hepatotoxic and carcinogenic in old-world monkeys.

Purification and characterization of a human lung tumor-associated antigen.

A human lung tumor-associated antigen was purified from a saline extract of a lung adenocarcinoma. The antigen was demonstrated in extracts of lung adenocarcinoma. The antigen was demonstrated in extracts of lung tumors with the use of an absorbed antiserum by double-diffusion immunoprecipitation. The antiserum did not react with extracts of normal lung or other normal tissues, and the antigen was immunologically distinct from other tumor-associated antigens. Purification was achieved by antibody affinity chromatography and preparative polyacrylamide gel electrophoresis. Isolation procedures were monitored by immunoreactivity with absorbed monospecific antiserum. The antigen was labeled with 125I and judged homogeneous by 1) polyacrylamide gel elecrophoresis in detergent and nondetergent gels, 2) molecular sieve chromatography, 3) ion exchange chromatography, and 4) sucrose gradient sedimentation analysis. A molecular weight of 77,000 was calculated from the s20.w value of 4.24S and from the D20.w value of 5.0X10(-7) cm2/sec. Sodium dodecyl sulfate gel electrophoresis indicated a subunit molecular weight of 42,000. The Stokes radius of the antigen was 40 A and the frictional ratio was 1.42, indicating a nonspherical molecule. The purified radioiodinated antigen could be quantitatively precipitated with specific antiserum.

Multiple markers for lung cancer diagnosis: validation of models for advanced lung cancer.

Sera from 171 patients with advanced lung cancer, from 110 normals, and from 123 subjects with benign respiratory diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen. Individual markers were studied, and optimal combinations of markers were sought for discriminating lung cancer patients from normals and from patients with benign lung disease. Numerous methods for combining the markers were examined, but the methods of logistic regression and recursive partitioning were finally adopted. The best discrimination rules we could find used only carcinoembryonic antigen (CEA) and total sialic acid (TSA). The performance of these rules was validated on an independent serum panel containing sera from 68 patients with advanced lung cancer, from 40 normals, and from 52 patients with benign respiratory disease. The combination rules based on TSA and CEA performed better than a rule based on CEA alone. Logistic discrimination rules with TSA and CEA that were designed to have 95% specificity achieved 54% sensitivity for discriminating advanced lung cancer from normal controls and 52% sensitivity for discriminating advanced lung cancer from controls with benign disease. Some aspects of clinical applicability are discussed, including planned studies for localized lung cancer and the requirement for further testing in specific clinical settings.

Multiple markers for lung cancer diagnosis: validation of models for localized lung cancer.

Sera from 71 patients with localized lung cancer, from 70 normal controls, and from 73 patients with benign lung diseases were analyzed for 10 substances to detect lung cancer: ferritin, lipid-bound sialic acid, total sialic acid, beta 2-microglobulin, lipotropin, the alpha and beta subunits of human chorionic gonadotropin, calcitonin (two assays), parathyroid hormone, and carcinoembryonic antigen (CEA). Individual markers were studied, and optimal combinations of markers were sought for discriminating patients with localized lung cancer from normal controls and from patients with benign lung disease. Both logistic regression and recursive partitioning methods for discrimination were tried. The best rules involved only CEA and ferritin for discriminating patients with lung cancer from normal controls, and CEA and age for discriminating patients with lung cancer from those with benign lung diseases. The performance of these rules was validated on an independent serum panel containing sera from 56 patients with localized lung cancer, 75 normal controls, and 75 patients with benign lung diseases. Three rules designed to achieve 95% specificity against normal controls attained 14%-36% sensitivity for localized lung cancer in the validation panels, whereas three rules designed to achieve 95% specificity against benign lung diseases attained 30%-39% sensitivity. Some aspects of potential clinical applications are discussed.

Tumor-associated antigen levels (carcinoembryonic antigen, human chorionic gonadotropin, and alpha-fetoprotein) antedating the diagnosis of cancer in the Framingham study.

Determinations of carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), and alpha-fetoprotein (AFP) were done by use of frozen serum samples antedating the diagnosis of cancer for 9 pancreatic and 8 gastric carcinoma patients from the Framingham Heart Study. The longest intervals for elevated antigens before cancer diagnosis were 10 months for CEA and 26 months for HCG. (The single elevated AFP was found in a sample 10 days before clinical diagnosis.) Samples from 31 controls matched with the cancer subjects by age, sex, vital capacity, and smoking status showed over 20% "false" positive CEA elevations (all smokers with low vital capacities) and over 20% borderline false positive HCG elevations in postmenopausal females. Although 10-26 months' lead time could infer some potential for use of these tumor-associated antigens to help detect malignant neoplasms at an earlier stage, a serious problem of frequent false positives prevents CEA and HCG levels from being useful as cancer-screening tests at this time.

Tumor markers for radiommunodetection of cancer.

One of the potential uses of tumor-associated antigens or tumor markers, the localization of metastatic tumors using radioactive antibodies, has now been demonstrated and confirmed in clinical situations. The next stage of development in radioimmunodetection will be the improvement of techniques and methodologies. The selection of the optimal marker or markers to be used for localization is one area where improvement will be forthcoming. Guidelines for the choice of potential markers and methods for evaluation of potential markers before being clinically tested are presented in this article.

Theoretical limitations in the immunodiagnostic imaging of cancer with computed tomography and nuclear scanning.

In order to help assess the feasibility of using immunologically tagged agents to render tumors detectable with current computed tomographic and nuclear scanners, mathematical formulations were developed to determine the theoretical limits of tumor detection relative to size and depth of the lesions. The results of our analysis suggest that visualization with computed tomography of a tiny tumor (1 sq mm, cross-sectional area) would require binding in the order of 2 x 10(5) iodine atoms/antigenic site, while imaging of a very large (900-sq mm) tumor would require approximately 10(4) atoms/site. Very low energy scanners might reduce these discouraging estimates by an order of 10(2). The immunological imaging of tumors with nuclear scanning appears quite feasible from our formulations, as has been demonstrated by others clinically. Small (1-sq cm) and deep (greater than or equal to 5-cm) tumors appear detectable with uptake ratios of the order of 5 or higher, which seem to be attainable currently. Smaller and deeper tumors require much higher uptake ratios to be detected.

Identification and purification of a human lung tumor-associated antigen from a primary lung tumor.

A human lung tumor-associated protein has been purified from an extract of a human small cell carcinoma of the lung and shown by Ouchterlony double diffusion analysis to be antigenically identical to a component which was previously demonstrated in 84 of 98 lung tumor extracts of all histological types but absent from extracts of normal adult and fetal lung, other normal tissues, and tumors of other organs. These studies utilized xenoantisera raised against a pool of lung tumor extracts which were exhaustively adsorbed with normal serum and tissue extracts. A radial immunodiffusion assay developed for the antigen permitted its quantitation throughout the course of isolation. Purification was accomplished by ion-exchange chromatography, gel filtration, and affinity immunoadsorption. By ion-exchange chromatography, the proteins appeared to be quite heterogeneous, with immunological reactivity detected in three different peaks. However, all the active components were immunologically identical. Gel filtration of the major antigenic component from diethylaminoethyl cellulose similarly demonstrated a further fractionation into several active, immunologically identical forms. These results suggest a charge-size isomeric relationship among the various forms, all of which possess a common and identical antigenic site. The major component was isolated throughout the purification scheme. The final product represented 9% of the input activity, produced a single, although broad, protein-staining region on 7% polyacrylamide gels which was coincident with antigenic activity, and exhibited immunological identity with the antigen in the crude extract as well as with that in an extract from another lung tumor.

Serum alpha-fetoprotein in patients with neoplasms of the gastrointestinal tract.

Serum alpha-fetoprotein levels were measured by a sensitive double-antibody radioimmunoassay in 580 patients with a variety of malignant and nonmalignant gastrointestinal diseases to determine the incidence of levels elevated above 40 ng/ml. Over 200 normal control subjects have all had levels below 40 ng/ml. Fifteen % of 95 patients with gastric carcinoma, 3 percent of 191 patients with colorectal carcinoma, 24 percent of 45 patients with pancreatic carcinoma, 25 percent of 8 patients with biliary tract carcinoma, and 70 percent of 73 patients with hepatocellular carcinoma had elevated serum alpha-fetoprotein. None of 14 patients with esophageal or small bowel carcinoma had elevated levels. In contrast, 1 percent of 154 patients with nonmalignant, nonhepatic gastrointestinal disease had elevations of serum alpha-fetoprotein. Alpha-Fetoprotein appears to be a potential marker for tumor activity in some patients with certain gastrointestinal cancers.

Characterization of a human lung tumor-associated antigen and development of a radioimmunoassay.

A human lung tumor-associated antigen (LTA), previously isolated from a small cell carcinoma, was further studied after labeling with N-succinimidyl-3-(4-hydroxy-5-[125I]iodophenyl)propionate. Two immunoreactive forms of the labeled antigen were observed and isolated after electrophoresis in 7% polyacrylamide gels. These components, referred to as LTA-I and LTA-II in order of mobility, were judged homogeneous by gel electrophoresis, G-200 gel filtration, size exclusion high-performance liquid chromatography, and sedimentation velocity analysis. The latter three techniques produced identical profiles for both forms of the LTA. Sephadex chromatography and high-performance liquid chromatography analyses indicated the mass of the antigens to be approximately 140,000 to 150,000 daltons with a D20,w of 4.2 to 4.3 x 10(-7) sq cm/sec. The S20,w values for both were 4.5 to 4.6S. Sodium dodecyl sulfate gel electrophoresis of LTA-II gave a single component with a molecular weight of 81,700, while LTA-I had a major component identical in size to LTA-II and two minor components with molecular weights of 50,000 and 27,700, respectively. The isoelectric point of LTA-II (peaks at pH 2.6 and 3.2) generally was more acidic than LTA-I (major component centered at pH 4.7, minor component centered at pH 3.1). A radioimmunoassay, with a useful detection range of from 1 to 100 ng/ml, was developed with LTA-I. This assay was used to determine the concentration of LTA in the sera of normal and lung cancer patients. Fifteen normal sera had a mean of 17 +/- 22 (S.D.) ng/ml, with none greater than 83 ng/ml (+3 S.D.). Thirteen lung cancer patients with Stage I (i.e., localized disease) had a mean of 187 +/- 219 ng/ml, with the means for 7 of 13 patients being greater than 83 ng/ml; 15 lung cancer patients with Stage III, more extensive disease, had a mean of 277 +/- 252 ng/ml, with the means for 12 of 15 patients being greater than 83 ng/ml. This antigen may be useful for the early detection or monitoring of lung cancer.

Quantitative assessments of the effect of bilateral subthalamic stimulation on multiple aspects of sensorimotor function for patients with Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of advanced Parkinson's disease. Most studies have evaluated the effectiveness of DBS of the STN using clinical motor scores or simple timed tests of motor function. There have been few studies that quantitatively assessed the outcome of STN DBS using multiple testing paradigms. In the current study, 11 patients who had bilateral STN DBS were quantitatively evaluated under four conditions using gait, postural control, and gait initiation. The four conditions included the medication on/stimulation on (M_on/S_on), medication on/stimulation off (M_on/S_off), medication off/stimulation on (M_off/S_on), and medication off/stimulation off (M_off/S_off) conditions. DBS of the STN significantly increased walking speed with and without levodopa, but had no influence on the cadence. The addition of levodopa had a minimal additional effect on walking speed. The effect of STN DBS on gait initiation approached the significant level. The mean values of lateral body sway during quiet standing increased moderately with medication and/or DBS, but the changes were not statistically significant. Future studies need to determine whether or not there is a potential negative effect of STN DBS on the postural control.

Sensitive and convenient quantitation of antibody binding to cellular antigens using glutaraldehyde preserved cells.

As a preliminary step in the identification and isolation of antibodies to human cancers, we have developed a sensitive and convenient assay for antibody binding to cellular antigens. The basis for the method is antibody binding to glutaraldehyde-fixed cells (AbGfC) and quantitation with radioiodinated staphylococcal protein A (SpA). Glutaraldehyde fixation of intact cells, which does not appear to effect the ability to form antigen-antibody complexes, provides a convenient and standard supply of target cells which may be stored at 4 degrees C and used in the assay over a period of several months. The amount of antibody specifically bound to the cells is quantitated by the addition of 125I-labeled SpA. The sensitivity of the method was compared with two complement-dependent cytotoxicity methods (trypan blue exclusion and 51Cr release assays) and tested with two antisera to human lung cancer and one antiserum to a membrane antigen of a murine lymphoma. These comparisons indicated much greater sensitivity when compared with the trypan blue exclusion assay and equivalent sensitivity with greater dose response characteristics when compared with the 51Cr release assay.

Prognostic factors in patients with hepatocellular carcinoma receiving systemic chemotherapy. Identification of two groups of patients with prospects for prolonged survival.

Among 37 patients with hepatocellular carcinoma given systemic chemotherapy, 12 (32 percent) lived 14 to 37 months from initiation of treatment whereas the remainder died within five months. Individual factors associated with improved survival included fully ambulatory performance status, lack of jaundice, response to chemotherapy, the fibrolamellar carcinoma pathologic variant, absence of cirrhosis, and normal serum alpha-fetoprotein levels. Patients living longer than 12 months fell into two groups. Seven patients with fibrolamellar carcinoma lacked evidence of hepatitis B serum markers or cirrhosis and had normal alpha-fetoprotein levels and surprisingly frequent extrahepatic metastases. All but one were Caucasians aged 25 years or less. The other five "long-term" survivors were all fully ambulatory without jaundice, and the majority were older non-Caucasians with tumor confined to the liver at the time of diagnosis and with hepatitis B markers, elevated alpha-fetoprotein levels, or cirrhosis. All patients without fibrolamellar carcinoma who were less than fully ambulatory or who had jaundice died quickly. Patients with fibrolamellar carcinoma have homogeneous clinical features, and their disease follows a relatively indolent course. In other patients with hepatocellular carcinoma, assessment of ambulatory status and serum bilirubin determination can identify those with some prospect of prolonged survival.