Effectiveness, safety and acceptability of no-test medical abortion (termination of pregnancy) provided via telemedicine: a national cohort study.

OBJECTIVE: To compare outcomes before and after implementation of medical abortion (termination of pregnancy) without ultrasound via telemedicine. DESIGN: Cohort analysis. SETTING: The three main abortion providers. POPULATION OR SAMPLE: Medical abortions at home at ≤69 days' gestation in two cohorts: traditional model (in-person with ultrasound, n = 22 158) from January to March 2020 versus telemedicine-hybrid model (either in person or via telemedicine without ultrasound, n = 29 984, of whom 18 435 had no-test telemedicine) between April and June 2020. Sample (n = 52 142) comprises 85% of all medical abortions provided nationally. METHODS: Data from electronic records and incident databases were used to compare outcomes between cohorts, adjusted for baseline differences. MAIN OUTCOME MEASURES: Treatment success, serious adverse events, waiting times, gestation at treatment, acceptability. RESULTS: Mean waiting time from referral to treatment was 4.2 days shorter in the telemedicine-hybrid model and more abortions were provided at ≤6 weeks' gestation (40% versus 25%, P < 0.001). Treatment success (98.8% versus 98.2%, P > 0.999), serious adverse events (0.02% versus 0.04%, P = 0.557) and incidence of ectopic pregnancy (0.2% versus 0.2%, P = 0.796) were not different between models. In the telemedicine-hybrid model, 0.04% were estimated to be over 10 weeks' gestation at the time of the abortion; all were completed safely at home. Within the telemedicine-hybrid model, effectiveness was higher with telemedicine than in-person care (99.2% versus 98.1%, P < 0.001). Acceptability of telemedicine was high (96% satisfied) and 80% reported a future preference for telemedicine. CONCLUSIONS: A telemedicine-hybrid model for medical abortion that includes no-test telemedicine and treatment without an ultrasound is effective, safe, acceptable and improves access to care. TWEETABLE ABSTRACT: Compelling evidence from 52 142 women shows no-test telemedicine abortion is safe, effective and improves care.

Comparison of ionised calcium measured using a portable analyser to a reference method in healthy dogs.

OBJECTIVES: To compare the ionised calcium measured on a portable analyser (iSTAT, Abbott) to a reference method. MATERIALS AND METHODS: Blood samples from 39 apparently healthy dogs were analysed in duplicate using a portable analyser and a reference method (Radiometer ABL800 FLEX). Bland-Altman plots and Passing-Bablok regression were used to assess constant and proportional bias between the two instruments. A within-assay percentage coefficient of variation and total error (TE) was calculated for both analysers. The reference interval was calculated for the portable analyser using the robust method with confidence interval bootstrapping. RESULTS: The Bland-Altman plot showed a -0.036 mmol/L difference between the two instruments (95% confidence limit -0.08 to 0.01 mmol/L; limits of agreement -0.07 to 0.006 mmol/L). Neither the Bland-Altman plot nor the Passing-Bablock regression (slope -0.03; 95% confidence interval -0.08 to 0.19 and intercept 1; 95% confidence interval 0.83 to 1.2) showed significant proportional bias. The coefficient of variation for the portable analyser was 1.08%, compared to 0.78% for the reference method with a total error of 3.5% for the portable analyser. The estimated population-based reference interval for ionised calcium using the portable analyser is 1.23 to 1.42 mmol/L. CLINICAL SIGNIFICANCE: For the healthy dogs in this study, compared to the reference method, the portable analyser showed no significant bias for measurement of ionised calcium. Further studies including hyper and hypocalcaemic dogs are required to determine clinical impact of the use of this analyser.

Disulfide bonding of a human prostate tumor-associated membrane antigen recognized by monoclonal antibody D83.21.

Previous reports from our laboratory have described the binding specificity of a monoclonal antibody, D83.21, prepared by fusing P3X63/Ag8 mouse myeloma cells with mouse lymphocytes immunized against the DU145 human prostate adenocarcinoma cell line. The D83.21 monoclonal antibody displayed preferential binding to human prostate and bladder carcinoma cell lines and tissues. This antibody was not reactive with a variety of other normal and malignant human cell lines or tissues. Immunofluorescence analysis indicated that the D83.21 antigen was located on the plasma membrane. Biochemical characterization of the target antigen was performed by subjecting detergent-soluble extracts of [3H]glucosamine-labeled cells to D83.21 monoclonal antibody affinity chromatography. The radioactive material that was specifically bound and eluted from the affinity column was analyzed by sodium dodecyl sulfate:polyacrylamide gel electrophoresis and fluorography. In the absence of 2-mercaptoethanol, the antigen displayed two prominent bands with molecular weights of 180 and 110 kilodaltons. In the reduced form, the antigen is composed of an Mr 60,000 heavy chain and an Mr 28,000 light chain. The antigen was further resolved using two-dimensional (intact/reduced) sodium dodecyl sulfate: polyacrylamide gel electrophoresis. These analyses indicated that the Mr 180,000 chain was composed entirely of Mr 60,000 subunits, whereas the Mr 110,000 band consisted only of Mr 28,000 subunits. The antigen recognized by the D83.21 monoclonal antibody is therefore a membrane glycoprotein with a subunit structure cross-linked together through disulfide bonds.

Tissue distribution and cellular location of the antigens recognized by human monoclonal antibodies 16.88 and 28A32.

Results from a previous study (M. V. Haspel et al., Cancer Res., 45: 3951-3961, 1985) indicated that it was possible to isolate a high proportion of human monoclonal antibodies reactive with cell surface, tumor-associated antigens when the hybridomas were obtained from fusions utilizing peripheral blood lymphocytes from patients immunized with autologous tumor cells. The assignment of membrane reactivity was made from immunoperoxidase studies which used air-dried, nonpermeabilized Cytospin preparations of colon tumor cells. Tumor specificity was assessed by immunohistological assays by using frozen sections of normal and malignant human tissues. We now describe a series of studies using two of these antibodies, 16.88 and 28A32, in which further information was obtained concerning the tumor specificity and cellular location of the target antigens reactive with these monoclonal antibodies. Data were acquired from a variety of experimental techniques which included quantitative and qualitative immunofluorescence on live and permeabilized cells, RBC-rosetting assays, immunoperoxidase studies on Cytospin and frozen tissue sections, and immunoblot procedures. These studies show that the 16.88 and 28A32 human monoclonal antibodies bind to antigens which (a) are located in the cell cytoplasm and are not expressed in detectable levels on the cell surface, and (b) are found in many normal and malignant cell types.

In vivo antitumor activity of a monoclonal antibody-Vinca alkaloid immunoconjugate directed against a solid tumor membrane antigen characterized by heterogeneous expression and noninternalization of antibody-antigen complexes.

It is widely believed that antigen heterogeneity and noninternalization of antigen-antibody complexes will severely limit the antitumor activity of monoclonal antibody-drug conjugates. The B72.3 monoclonal antibody binds to a tumor-associated antigen which is heterogeneously expressed in human carcinomas (J. Schlom, Cancer Res., 46: 3225-3238, 1986). We therefore performed studies to assess the degree of internalization of B72.3 antibody-antigen complexes and the level of in vivo antitumor activity that could be achieved with B72.3 conjugated to 4-desacetyl vinblastine-3-carboxhydrazide. Internalization studies were performed on LS174T colorectal carcinoma and OVCAR-3 ovarian carcinoma cells using iodinated B72.3 as well as an iodinated antibody that binds to the human transferrin receptor, IIB21. These data indicated that, in contrast to HB-21, the B72.3 antigen-antibody complex was not internalized. The B72.3-Vinca alkaloid immunoconjugate demonstrated significant antitumor activity against LS174T xenografts, although complete regressions of established tumors were not achieved. Immunohistochemical analyses indicated that the B72.3 antigen was heterogeneously expressed in the LS174T xenografts and that tumor cells which were not killed by high doses of B72.3-Vinca also expressed the B72.3 antigen. These studies indicated that significant antitumor activity may be achieved by monoclonal antibody-drug conjugates even when antigen heterogeneity and noninternalization of antigen-antibody complexes are encountered. The data also suggested that the formulation of antibody-drug conjugate cocktails to counteract antigen heterogeneity may not be sufficient to eradicate all malignant cells within a solid tumor mass.

Site-specific prodrug activation by antibody-beta-lactamase conjugates: regression and long-term growth inhibition of human colon carcinoma xenograft models.

Antibody-directed catalysis (ADC) is a two-step method for the delivery of chemotherapeutic agents in which enzyme-antibody conjugate, prelocalized to antigen-bearing tumor cells, catalyzes the site-specific conversion of prodrug to drug. An ADC system consisting of F(ab')-beta-lactamase conjugates and a cephalosporin derivative of the oncolytic agent 4-desacetylvinblastine-3-carboxhydrazide was investigated. The ability of the system to mediate antitumor activity was compared with that of free drug given alone and with covalent drug-antibody conjugates in LS174T and T380 colon carcinoma xenografts in nude mice. Efficacy increased from moderate tumor growth inhibition by using free 4-desacetylvinblastine-3-carboxhydrazide to tumor regression and long-term stabilization with the ADC system. Labile covalent drug-antibody conjugates prepared from the same antibodies were less effective than ADC and required much higher antibody doses. The antigens KS1/4, carcinoembryonic antigen, and tumor-associated glycoprotein-72, TAG-72, present on the model cell lines, were chosen to investigate the effect of differences in subcellular location and expression heterogeneity on the efficacy of ADC delivery. Response was equivalent with the three tumor antigens. Hence, heterogeneous expression and membrane shedding of carcinoembryonic antigen and TAG-72, did not diminish the suitability of these antigens as targets for ADC therapy. In contrast, drug-antibody conjugate efficacy was more sensitive to subcellular location and heterogeneity. Thus, ADC is a highly effective form of immunochemotherapy in preclinical models, with applicability toward a variety of antigen targets.

Development of a dual label fluorescence technique that can be utilized to elucidate the mechanism of action of monoclonal antibody-drug conjugates.

A method is described that allows the simultaneous visualization and relative assessment of both the antibody and drug components of monoclonal antibody-drug conjugates at the target cell membrane. The antibody is detected by a fluorescein-conjugated anti-mouse immunoglobulin serum while the drug is visualized by rhodamine avidin or phycoerythrin-streptavidin binding to a biotinylated anti-Vinca alkaloid monoclonal antibody. This technique was effective in demonstrating the cell surface localization of a monoclonal antibody-Vinca alkaloid conjugate to human lung adenocarcinoma cells grown in vitro and was also used to demonstrate targeting of the conjugate in vivo to the membranes of these same tumor cells grown as a nude mouse xenograft. This method was also utilized to help elucidate the mechanism of action of monoclonal antibody-drug conjugates.

Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979.

Overexpression of P-glycoprotein (Pgp) by tumors results in multidrug resistance (MDR) to structurally unrelated oncolytics. MDR cells may be sensitized to these oncolytics when treated with a Pgp modulator. The present study evaluates LY335979 as a modulator both in vitro and in vivo. LY335979 (0.1 microM) fully restored sensitivity to vinblastine, doxorubicin (Dox), etoposide, and Taxol in CEM/VLB100 cells. LY335979 modulated Dox cytotoxicity even when LY335979 (0.5 microM) was removed 24 h prior to the cytotoxicity assay. LY335979 blocked [3H]azidopine photoaffinity labeling of the M(r) approximately 170,000 Pgp in CEM/VLB100 plasma membranes and competitively inhibited equilibrium binding of [3H]vinblastine to Pgp (Ki of approximately 0.06 microM). Treatment of mice bearing P388/ADR murine leukemia cells with LY335979 in combination with Dox or etoposide gave a significant increase in life span with no apparent alteration of pharmacokinetics. LY335979 also enhanced the antitumor activity of Taxol in a MDR human non-small cell lung carcinoma nude mouse xenograft model. Thus, LY335979 is an extremely potent, efficacious modulator that apparently lacks pharmacokinetic interactions with coadministered anticancer drugs and is, therefore, an exciting new agent for clinical evaluation for reversal of Pgp-associated MDR.

Immunohistochemical localization of prostate carcinoma-associated antigens.

The immunoperoxidase technique was used to study the localization and distribution of antigens reactive with two monoclonal antibodies, D83.21 and P6.2, produced against cultured prostate tumor cells, in formalin-fixed, paraffin-embedded histological sections of human tissues. Monoclonal D83.21 reacted with 11 of 19 (58%) primary prostate carcinomas and 1 of 6 (17%) metastatic tumors, whereas monoclonal P6.2 reacted with 14 of 19 (68%) primary and 4 of 6 (67%) metastatic prostate tumors. Neither antibody reacted with five primary prostate tumors and one metastatic prostate tumor. In some tumor cells, the antigens recognized by these monoclonals were localized in either the cytoplasm or cell membrane, while in other tumor cells, both diffuse cytoplasmic and membrane or focal staining patterns were observed. In addition to the variable staining patterns, antigenic heterogeneity was also noted within most prostate tumors examined. Two types of staining variability were observed: (a) tumor cells in one area of the tissue section stained positive, but in another area they did not react with the antibody; and (b) both stained and unstained tumor cells were adjacent to each other. These results would suggest that a panel of monoclonals will be required to detect the different subpopulations of prostate tumor cells. Neither antibody reacted with 6 normal or 12 benign prostate tissues, nor any of a variety of other normal human tissues except for staining of the proximal tubules of normal kidneys. The antigen detected by P6.2 demonstrated a wider tissue distribution being found on bladder, breast, lung, and pancreatic tumors, whereas the antigen recognized by D83.21 was restricted to prostate and bladder carcinomas. These antibodies may have clinical applicability for the identification of prostate tumor cells in biopsy specimens and for immunohistopathological classification of prostate carcinomas.

Monoclonal antibodies to human prostate and bladder tumor-associated antigens.

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.

Human prostate tissue antigens defined by murine monoclonal antibodies.

BALB/c mice were hyperimmunized against a membrane preparation derived from a pool of transurethral resection specimens which included three benign prostatic hyperplasia and one prostate adenocarcinoma tissue samples. The activated lymphocytes were fused with the NS-1 mouse myeloma cell line, and supernatants from immunogen-reactive hybridomas were screened for antibody binding activity using a solid-phase radioimmunoassay against the Calu-1 human lung adenocarcinoma cell line and several membrane preparations derived from various normal human tissues. Hybridoma cultures secreting antibodies which did not appear cross-reactive were doubly cloned by limiting dilution and screened against a large panel of membrane preparations derived from normal prostate, benign prostatic hyperplasia, and prostate adenocarcinoma tissues as well as samples obtained from a variety of normal human tissues. The monoclonal antibodies were also evaluated against 24 normal, virally transformed, and malignant human cell lines. Two monoclonal antibodies were isolated which demonstrated a restricted binding activity to prostate antigens and were not widely cross-reactive with nonprostate normal tissues or cell lines. These antibodies were designated TURP-27 (IgG3, k) and TURP-73 (IgG2a, k). Both of these monoclonal antibodies were reactive against formalin-fixed, paraffin-embedded tissues in the immunoperoxidase assay and were subsequently tested against a variety of normal, hyperplastic, and malignant human tissues. These studies indicated that TURP-27 may be directed against a new prostate organ-associated marker and that TURP-73 is directed against an antigen expressed on prostate and a limited number of other tissues.

In vivo selection of human tumor cells resistant to monoclonal antibody-Vinca alkaloid immunoconjugates.

UCLA-P3 human lung adenocarcinoma cells were grown in nude mice and given repetitive treatments of a monoclonal antibody-Vinca alkaloid immunoconjugate. Although this therapy resulted in a greater than 4-fold reduction in mean tumor mass of the established tumors, some animals experienced a reinitiation of tumor growth after cessation of conjugate treatment. Two such animals were treated again with high doses of monoclonal antibody-Vinca but one of the tumors was no longer regressed by the drug conjugate. The tumor was excised, enzymatically dissociated, and grown in tissue culture. Cultured cells were reimplanted in nude mice and subjected to further therapy with a monoclonal antibody-Vinca conjugate. The resulting tumors were also refractory to the immunoconjugate therapy. This cycle was repeated for a total of three times and resulted in the serial in vivo selection of three conjugate resistant variants. The mechanism responsible for the in vivo resistance of human tumor cells to the monoclonal antibody-Vinca immunoconjugate is unknown but does not appear to involve antigen modulation, altered tumor cell growth rate, or an apparent decrease in tumor targeting in vivo. The resistance was also not accompanied by any detectable elevation in multidrug resistance 1 mRNA or P-glycoprotein expression. Significantly, the resistance pattern was observed only in vivo and was not maintained by cells grown in vitro.

Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer.

Arzoxifene ([6-hydroxy-3-[4-[2-(1-piperidinyl)-ethoxy]phenoxy]-2-(4-methoxyphenyl)]benzo[b]thiophene) is a selective estrogen receptor modulator (SERM) that is a potent estrogen antagonist in mammary and uterine tissue while acting as an estrogen agonist to maintain bone density and lower serum cholesterol. Arzoxifene is a highly effective agent for prevention of mammary cancer induced in the rat by the carcinogen nitrosomethylurea and is significantly more potent than raloxifene in this regard. Arzoxifene is devoid of the uterotrophic effects of tamoxifen, suggesting that, in contrast to tamoxifen, it is unlikely that the clinical use of arzoxifene will increase the risk of developing endometrial carcinoma.

Effects of iodine intake on thyroid secondary lysosomes after subtotal thyroidectomy.

This study tested the effects of different iodine intakes on thyroid ultrastructure and function in thyroid remnants after subtotal thyroidectomy (sub-tx). Removal of most of the thyroid gland causes an elevation of endogenous TSH, which chronically stimulates the residual tissue. Male Sprague-Dawley rats were divided into three groups; Low Iodine Group (LIG), Moderate Iodine Group (MIG), and High Iodine Group (HIG). There was no significant difference among total thyroid weights removed by sub-tx, but thyroid remnant weights and TSH levels were higher at death (6 weeks after sub-tx) in LIG than in MIG and HIG. Total specific activities of cathepsin D and of arylsulfatase A in the sedimentable and nonsedimentable subcellular fractions were at least 38% lower in LIG than in MIG and HIG. The ratio between relative follicular volume and colloid volume determined by morphometry was higher in LIG than in MIG and lower in HIG than in MIG. Ultrastructurally, the relative volume occupied by secondary lysosomes was higher in HIG than in MIG, whereas the number of secondary lysosomes was not higher in LIG than in controls. Autoradiographic studies with 125I revealed that a large part of the radioactivity was in thyroid cell secondary lysosomes in MIG and HIG when radioiodine was injected 3 weeks before death. It is concluded that after sub-tx, iodine 1) regulates the weight of thyroid remnants, perhaps only indirectly through TSH, 2) modulates the number of secondary lysosomes in thyroid cells, and 3) slows down the turnover of secondary lysosomes. An iodine-deficient regimen impedes the secondary lysosomes to increase. Because of these findings, we postulate that chronic TSH stimulation along with a possible toxic role of iodine after sub-tx could induce an accumulation of lysosomal bodies.

Thyroid lysosomal enzyme activity and ultrastructure after subtotal thyroidectomy.

Subtotal thyroidectomies were performed in rats to increase the level of endogenous TSH, creating a condition of chronic TSH stimulation. The activities of various classes of lysosomal enzymes (cathepsin D, beta-glucuronidase, and aryl sulfatase A) were studied in thyroid tissue remaining in situ at various time intervals after subtotal thyroidectomy (sub-tx). These alterations were correlated with morphometric and ultrastructural changes in tissue lysosomes and with serum T4 and TSH. Specific activities of all three lysosomal enzymes were elevated in the residual tissue as compared with those in control tissue during 7 weeks after sub-tx in the first experiment. In the second experiment, the activities of all three enzymes were elevated both 3 and 6 weeks after sub-tx, and the activities of cathepsin D and aryl sulfatase A in the postnuclear homogenate (S2) were significantly elevated. Plasma TSH was elevated and T4 was decreased both 3 and 6 weeks after sub-tx. The results of the third experiment determined that there were significant alterations in nuclear cytoplasmic ratios as well as in the number, area, and volume density of lysosomes in both groups compared with respective control values. In addition, both lysosomal area and volume density in animals 6 weeks after sub-tx were significantly larger than those in animals 3 weeks after sub-tx. We conclude that chronic stimulation of residual thyroid tissue 6 weeks after sub-tx causes alterations in lysosomal ultrastructure as well as in lysosomal enzyme activity.

Reversal of multidrug resistance by the P-glycoprotein modulator, LY335979, from the bench to the clinic.

Multidrug resistance may be conferred by P-glycoprotein (Pgp, ABCB1) or the multidrug resistance associated protein (MRP). These membrane proteins are members of the ATP binding cassette transporter superfamily and are responsible for the removal from the cell of several anticancer agents including doxorubicin. Modulators can inhibit these transporters. LY335979 is among the most potent modulators of Pgp with a Ki of 59 nM. LY335979 is selective for Pgp, and does not modulate MRP-mediated resistance by MRP1 (ABCC1) and MRP2 (ABCC2). LY335979 significantly enhanced the survival of mice implanted with Pgp-expressing murine leukemia (P388/ADR) when administered in combination with either daunorubicin, doxorubicin or etoposide. Coadministration of LY335979 with paclitaxel compared to paclitaxel alone significantly reduced the tumor mass of the Pgp-expressing UCLA-P3.003VLB lung carcinoma in a xenograph model and delayed the development of tumors in mice implanted with the parental drug-sensitive UCLA-P3 tumor. LY335979 was without significant effect on the pharmacokinetics of these anticancer agents. This may be due impart to its poor inhibition of four major cytochrome P450 isozymes important in metabolizing doxorubicin and other oncolytics. The selectivity and potency of this modulator allows the clinical evaluation of the role of Pgp in multidrug resistance. LY335979 is currently in clinical trials.

New antitumor monoclonal antibody-vinca conjugates LY203725 and related compounds: design, preparation, and representative in vivo activity.

A method has been developed to allow the direct coupling of the cytotoxic vinca alkaloid 4-desacetylvinblastine-3-carbohydrazide (DAVLB hydrazide) to a variety of murine monoclonal antibodies directed against human solid tumors. Periodate oxidation of carbohydrate residues on the antibodies, followed by reaction with DAVLB hydrazide in aqueous acid affords, in most cases, conjugates with conjugation ratios of 4-6 vincas per antibody in high yield without significantly impairing antigen binding or solubility. The outcome of the conjugation reaction is highly dependent on the concentration of, and time of exposure of the protein to, the oxidant. These conjugates exhibit potent antitumor activity in vivo against a number of human solid tumor-nude mouse xenografts, with efficacy and safety increased over unconjugated DAVLB hydrazide. This antitumor activity is also superior to that of similarly prepared but nontarget tumor binding antibody-DAVLB hydrazide conjugates. MoAb-DAVLB hydrazide conjugates release DAVLB hydrazide in solution in a temperature- and pH-dependent manner. Hydrolytic release of unmodified DAVLB hydrazide from tumor-localized MoAb-DAVLB hydrazide conjugates in vivo may be an important factor in their antitumor activity.

A statistical evaluation of the binding of ferritin-conjugated lectins to the surface of rat cells. Topographical variations as a function of lectin concentration and cell type.

Statistical procedures were utilized to evaluate the concentration dependence of labeling by ferritin-conjugated lectins on four different rat cells: hepatocytes, normal thymocytes, Friend virus-induced rat tumor cells and feline sarcoma virus-induced rat sarcoma cells. Labeling by ferritin conjugates of concanavalin A, wheat germ agglutinin and Ricinus communis agglutinins I and II was quantitated by counting the number of ferritin granules on 600 Angstrom membrane segments. Relationships between the arithmetic means and variances for sample populations from each cell and ferritin-lectin combination were used to define four types of topographical distributions: uniform/ordered, uniform/random, random and clustered. It was found that the distribution and/or density of surface-bound lectin was concentration-dependent for all four ferritin-lectins. The nature of this dependency was complex and varied with both lectin and cell type.

Update of ocular reticulum cell sarcoma.

Reticulum cell sarcoma involving the vitreous and the brainstem occurred in a 45-year-old man. He initially was seen with diplopia from a partial left-sided third cranial nerve palsy, which is rare. Later, a typical uveitis developed in the right eye. An initial diagnosis of brainstem glioma, based primarily on the computed tomographic scan findings and clinical history, was ultimately proved erroneous when the correct diagnosis was shown by the results of a cytologic examination of vitreous aspirate. Excellent visual response to a moderately high oral dose of steroids occurred, which has not been usual in other reported cases. Definitive cobalt (gamma) radiation therapy (6,000 rad to the brainstem and 4,000 rad to the vitreous) has produced a one-year remission at this time.

Treatment of nontoxic megacolon by colonoscopy.

The indications for colonoscopy in a recent consecutive series of 232 examinations were analyzed. Of these examinations, 30 (13%) were performed for nontoxic megacolon. Nontoxic megacolon is defined as severe dilatation of a segment or the entire colon unaccompanied by signs or symptoms of colon toxicity. Mechanical factors (volvulus, anastomosis, diverticulosis, carcinoma) were responsible for the nontoxic megacolon in 13 of these patients. Nontoxic megacolon was classified as secondary to acute pseudoobstruction (Ogilvie's syndrome, pancolonic megacolon, acute myxedema ileus) in 17 patients. All patients were being evaluated for possible exploratory celiotomy to prevent perforation of the colon because of the massive colonic distention. Colonoscopic examination was performed at the bedside or in the intensive care unit for 11 of 30 patients. No bowel preparation was used. Evacuation of air and fecal material was more efficiently accomplished by use of an external suction device attached to the biopsy part of the endoscope. For 12 of the 13 patients who had a mechanical basis for their nontoxic megacolon the colon was successfully decompressed. All 17 patients with acute pseudoobstruction were successfully treated. There were no iatrogenic perforations. Possible emergency operation was avoided for all patients except one who had a cecal volvulus. Colonoscopy should be considered as the initial treatment for nontoxic megacolon prior to surgical intervention.