Complications of intraarticular calcaneal fractures.

The treatment of intraarticular calcaneal fractures remains a controversy in orthopaedics because of the associated complications. The authors present a systematic review of complications associated with calcaneal fractures. A MEDLINE search was conducted to review the results of operative and nonoperative treatment of calcaneal fractures to determine the most common complications reported. The following were reported to be the most common complications: swelling and fracture blisters, compartment syndrome, wound dehiscence and infection, neurovascular injury, tendon injury, heel pad pain and heel exostosis, malunion, and arthritis. Each complication was reviewed as to etiology, incidence, diagnosis, prevention, and treatment. Increased awareness of these complications and their prevention will aid the practitioner in decision-making and result in better treatment outcomes for this fracture.

Immunohistochemical analysis of pulmonary and pleural tumors with the monoclonal antibody HYB-612 directed against the multidrug resistance (MDR-1) gene product, P-glycoprotein.

In this study, 212 untreated primary pulmonary and pleural neoplasms were studied immunohistochemically with the monoclonal antibody HYB-612 which detects the multidrug resistance (MDR)-related P-glycoprotein (gp180). A tumor was considered positive for the expression of the MDR phenotype, even if a single rare positive cell was detected. Using this criterion, all of the various histologic subtypes were found to express MDR to varying degrees. The frequency of expression of this phenotype was found to be notably higher in non-small-cell carcinomas than in small-cell carcinomas. These findings are consistent with the known clinical responses of these neoplasms. The detection of gp180 in untreated lung neoplasms may be predictive of the responsiveness of neoplasms to chemotherapeutic agents. In addition, its presence or absence might be useful in determining the appropriate treatment protocol for given patients.

Smoking cessation through cigarette-fading, self-recording, and contracting: treatment, maintenance and long-term followup.

Seven adult subjects, all with extensive smoking histories, participated in a smoking cessation program. Intervention procedures included cigarette-fading, self-recording, and contracting. A changing-criterion analysis showed that six of the seven subjects were able to abstain from smoking within two months of intervention. The seventh subject was able to meet two changes in criterion, but dropped out of the treatment programme during the third. Of the sex remaining subjects, five were able to abstain from smoking during the six-month maintenance period. The sixth subject resumed smoking in the fourth month of maintenance and preferred to continue smoking thereafter. Followup data, collected every three months for two years, showed that the five remaining subjects were able to abstain from smoking for two years following the cessation of the maintenance programme.

Monoclonal antibodies as reversible equilibrium carriers of radiopharmaceuticals.

We have prepared monoclonal antibodies (MoAbs) with the specific ability to bind metal chelates such as 111In benzyl EDTA. One, 10, 50 and 100 micrograms MoAb CHA255 Kb = 4 X 10E9 was complexed with 111In BLEDTA II, BLEDTA IV, and benzyl EDTA and injected i.v. in Balb/c mice with KHJJ tumor. The biological half-life by whole body counting was profoundly altered for all three compounds; from minutes to hours with 10 micrograms; to days with 100 micrograms. Tumor uptake increased 50 fold at 24 h with increasing MoAb but satisfactory tumor concentrations (3% per g) and tumor/blood ratios (1.8:1) were obtained with an amount equivalent to 7 mg for a human. Blood level and whole body activity were decreased 30-50% within 3 h or i.v. injection of a "flushing" dose of unlabeled indium benzyl EDTA, increasing tumor/blood ratios to 50:1.

Antibodies against metal chelates.

Because monoclonal antibodies can recognize and bind to specific groups of atoms such as tumour antigens, they have promise for use in vivo as carriers of radionuclides, drugs or other appended molecules for diagnosis and treatment of disease. Attachment of metal ions to antibodies by means of bifunctional chelating agents can add the diverse nuclear, physical and chemical properties of the metallic elements to these specific binding proteins (ref. 4 and refs therein). With the ultimate aim of engineering probe-binding properties into the antibodies themselves, we have now prepared monoclonal antibodies against the EDTA chelate of indium. These antibodies show a remarkable preference for indium chelates; changing to another metal such as scandium or gallium can decrease the antibody-binding constant by more than three orders of magnitude. These antibodies also introduce a new degree of control over the biological distributions of chelated radionuclides, markedly altering their uptake in tumours and normal organs.

Characteristics of membrane and cytosol forms of the mammary tumor glycoprotein molecule MTGP in human breast carcinoma cell cultures and tumors.

The presence, concentration and selected molecular characteristics of the human mammary carcinoma glycoprotein molecule set MTGP, a trace and apparently tumor-specific molecule, were examined in fifteen cell cultures established from mammary carcinomas, tissue from seven mammary carcinomas and control cultures. Both cytosol and membrane-associated forms of MTGP were analyzed, and each was phenotyped by reference to isoelectric point and buoyant density. All cells or tissues of mammary carcinoma origin contained membrane MTGP, whereas cytosol MTGP was undetectable in cell cultures from half of the mammary carcinomas. Neither membrane nor cytosol MTGP were detectable in cells other than mammary carcinomas. Cytosol MTGP could be assigned to three groups by reference to presence, isoelectric point and buoyant density. Membrane MTGP also exhibited heterogeneity between different tumors and could be assigned to three groups by isoelectric point and buoyant density. Each form of MTGP was homogeneous for a given single tumor or cell culture and retained its phenotypic features with passage and cloning. Four general types of MTGP are proposed, through there may be additional fine heterogeneity that cannot be further resolved at this time. These data provide an initial characterization of the membrane form of MTGP and an integrated characterization that is consistent with the concept that tumor-specific antigens may possess both constant regions by reference to antigens recognized by the antisera and variable structure by reference to physicochemical characteristics.

Radioimmunoassay for tissue distribution of a human mammary tumor-specific glycoprotein.

The candidate tumor-specific soluble mammary tumor glycoprotein with a molecular weight of approximately 20,000 (MTGP20) has been isolated from human breast carcinomas and characterized biochemically. Although with the use of xenoantisera this glycoprotein has previously been demonstrated only in breast carcinomas, analyses of body fluids and conclusions regarding putative tumor specificity have been limited by the sensitivity of assays. In the present study, a specific radioimmunoassay has been developed. With appropriate selection of buffer, the assay has a sensitivity threshold of less than 0.1 unit of MTGP20 per ml, equivalent to less than 250 pg type I MTGP20 per ml or less than 530 pg type II MTGP20 per ml, which is more than 200-fold more sensitive than previously described assays. MTGP20 type I, which contains tyrosine, was labeled with 125I and used as the immunochemical ligand in a double antibody competitive inhibition assay. A partial weak cross-reaction was observed with a mixture of placental glycoprotein (perchloric acid extract), but this reaction was abolished by absorption of antisera with placental glycoprotein. Normal tissue and tumors of other than breast origin were devoid of MTGP20-related antigens. MTGP20-related antigens were not detectable in sera or concentrated urine specimens from normal individuals or patients with metastatic breast carcinomas. The present studies further support the probable tumor specificity of this glycoprotein but indicate that it does not represent a circulating secretory product of the cancer cell and does not provide a serum marker for breast carcinoma.

Subcellular localization of the sedimentable form of mammary tumor glycoprotein to the tumor cell plasmalemma.

A form of mammary tumor glycoprotein (MTGP) has been observed to be associated with the sedimentable fraction of homogenates of human carcinomas of the breast. A MTGP-containing breast carcinoma cell line, HS-578T (AY-726), containing both soluble and sedimentable forms of MTGP, was fractionated by differential ultracentrifugation, discontinuous sucrose gradient and on a polyethylene glycol-dextran gradient. The separated crude nuclei fraction, crude mitochondrial fraction, disrupted organelles, ribosomes and rough microsomes, smooth microsomes, and plasmalemma were characterized by electron microscopy and enzymatic markers which confirmed that each fraction was highly enriched in the respective subcellular constituents. Analysis of insoluble MTGP demonstrated significant coisolation with the plasmalemma. On the basis of the present data showing that the sedimentable form of MTGP is firmly associated with the plasmalemma and previous evidence showing the specificity of MTGP for breast carcinoma cells and the surface exposure of MTGP on viable cells, we conclude that sedimentable MTGP is an integral membrane glycoprotein that could have biological significance in the behavior or immunobiology of these tumors.

Colonic tumor membrane-associated glycoprotein: isolation of antigenically-active peptides after chemical cleavage.

A membrane-associated glycoprotein fraction, referred to a CEA-M was isolated from human colonic tumor tissue by sodium dodecyl sulfate extraction of membrane fragments followed by wheat germ agglutinin affinity chromatography, Bio-Gel A-1.5 gel filtration and preparative slab gel electrophoresis. With a m.w. of approximately 200,000, isoelectric point of about 4.2 and carbohydrate:protein ratio of 2:1, this glycoprotein has physiocochemical and antigenic similarities to carcinoembryonic antigen, CEA. Immunochemical studies have shown that antiserum developed for this glycoprotein possesses relative specificity for human colonic carcinomas. Chemical cleavage of this glycoprotein by 2-nitro-5-thiocyanobenzoic acid resulted in three major Coomassie Blue and two periodic acid Schiff stainable fragments (one of which stains with both). It was found that one of the glycopeptides, labeled as TA, isolated by affinity and covalent chromatography, contained 77% carbohydrates and possessed antigenic determinants recognized by at least 70% of the antibody population raised against the total glycoprotein fraction; purified antibodies to this region of the molecule seem promising for the development of a specific assay for gastrointestinal tumors.