Combined therapy for cancer of the anal canal

Nineteen patients with squamous-cell cancer of the anal canal have been treated with combined chemotherapy and radiation therapy, followed by appropriate surgery. The authors are convinced that the combined therapy is effective enough to avoid abdominoperineal resection if disappearance of the lesion is proven by adequate examination and biopsy. Although they believe cancers 5 cm or less in maximum diameter are generally adequately managed in this manner, experience is still too limited to justify, a recommendation, to change currently accepted management. Read at the meeting of the American Society of Colon and Rectal Surgeons, Hollywood, Florida, May 11 to 16, 1980. This paper received the New York Society of Colon and Rectal Surgeons Award.     

The site‐specific epidemiology of hip fracture in the Australian Capital Territory with projections for the first half of the 21st century: Implications for clinical management and health services planning

Objectives: To analyse the site‐specific epidemiology of hip fracture (HF) for the ACT and to project HF up to 2051. Methods: Age‐ and sex‐specific rates of HF and projections of the number of HFs were calculated by applying the age‐ and sex‐specific rates to the median population projections. Results: Analysis of patterns of HF by anatomical site of fracture revealed a diverse relationship according to age and sex. Fracture rates were higher in men before age 60 (1.8 : 1), and thereafter in women (3.1 : 1). In the age group of 60–64 years, the female : male ratio was 8.2 : 1 for cervical versus 1.8 : 1 for trochanteric fractures. Treatment for osteoporosis was under‐utilised. HF in people aged > 60 years will almost double by 2011, and increase 2.5‐fold and 5.4‐fold by the years 2021 and 2051, respectively. The greatest increase will occur in older men. Conclusions: The number of HFs in the first half of the 21st century will increase dramatically. Aetiological and pathophysiological differences in HF emphasise the need to individualise preventative strategies.     

Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(- )-inhibitor complexes in sepsis

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.     

Antibodies reactive with human T cell leukemia viruses in the serum of hemophiliacs receiving factor VIII concentrate

The third member of the family of T cell leukemia viruses (HTLV III) has been proposed as the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). A high risk of AIDS has been reported among patients with hemophilia, particularly those with factor VIII deficiency who receive commercial clotting factor concentrates. In a prevalence survey conducted between September 1982 and April 1984, initial serum samples from 74% of hemophiliacs who had ever been treated with commercial factor VIII concentrate, 90% of those frequently treated with factor VIII concentrate, and 50% of those treated with both factor VIII and factor IX concentrates had antibodies reactive against antigens of HTLV III, compared with none of the hemophiliacs treated only with factor IX concentrate or volunteer donor plasma or cryoprecipitate. Two of the seropositive patients have developed AIDS-related illnesses, and a third patient died of bacterial pneumonia. One initially seronegative patient developed antibodies against HTLV III during the study and is currently well. The predominant antibody specificities appear directed against p24 and p41, the presumed core and envelope antigens of HTLV III, suggesting that factor VIII concentrate may transmit the p24 and p41 antigens of HTLV III. However, the presence of infectious retroviruses in clotting factor concentrates and the effectiveness of screening and viral neutralization procedures remain to be determined.     

A rat model for studying colonic cancer: Effect of cholestyramine on induced tumors

Summary Dimethylhydrazine, azoxymethane, and methylazoxymethanol are highly efficient intestinal carcinogens in the rat. Azoxymethane is the best, producing tumors in all rats. The lesions occurred in significant numbers in the small intestine when given at high dosage levels over a period of six months or more. The tumors tend to occur more in the proximal halves of both segments of the intestine. When the animals are fed a 2 per cent cholestyramine diet, there is a marked increase in the tumor yield and the increase is, for the most part, in the large intestine, especially its distal half. Investigations of the mechanisms whereby cholestyramine enhances tumor formation in the large intestine of the rat are continuing. We conclude that the rat given azoxymethane subcutaneously at weekly intervals while on a 2 per cent cholestyramine diet is an excellent experimental model for studies of colonic cancer. Read at the meeting of the American Proctologic Society, New York N. Y., June 11 to 14, 1972. Supported by Matilda R. Wilson Fund.     

Prospects for the prevention of colorectal cancer

Cancer research has been productive in developing new knowledge on the role of diet in cancer. It is clear from epidemiologic observations that diet is the principal factor in the cause of colorectal cancer in most people. Therefore, a significant reduction in incidence is possible in countries where the disease is common. The ingestion of excessive amounts of fat appears to be the major factor that promotes cancer development. Animal studies confirm this and have recently shown that the sources of fat vary in the degree of their promotional effect. Fiber is generally considered to inhibit cancer but it is now clear that only some types of fiber are effective. These include whole grain cereals, and fruit and vegetables containing large amounts of uronic acid. In addition to fiber, a number of micronutrients, chemicals, and drugs have been found to be effective inhibitors. It is clear that the basic information concerning dietary changes that can reduce colorectal cancer incidence in this country has been uncovered. Additional information is needed about specific details of dietary guidelines. These include identification of the best mixture of sources of fat and how to incorporate such a mixture in the diet. Substances in foods need to be identified that, when included in the diet, help to lower cancer risk. People at high risk may require an additional supplement of inhibitors. New epidemiologic studies and human intervention trials should provide the necessary information to design dietary guidelines that are more specific than current ones.     

An important role for the alpha 1,3 fucosyltransferase, FucT-VII, in leukocyte adhesion to E-selectin

E-selectin is an adhesion molecule expressed on the surface of activated endothelial cells, which has been shown to be important in the initial steps of leukocyte extravasation into inflamed tissues. E- selectin binds neutrophils, monocytes, eosinophils, basophils, natural killer (NK) cells, and subsets of lymphocytes, although the precise ligand(s) on these cells have not been identified. Several studies have proposed certain carbohydrate structures, including sLex and related structures, as E-selectin ligands. In contrast to these studies, we report here the identification of several human B cell lines that exhibit binding to E-selectin without expression of any of the previously identified E-selectin binding carbohydrate epitopes. The unique carbohydrate phenotype of these B cell lines suggests that they may express a novel, sialylated carbohydrate structure(s) that binds to E-selectin. To investigate the enzymatic basis of this novel form of E- selectin binding, we examined the expression of the two principal leukocyte alpha 1,3 fucosyltransferases, FucT-IV and FucT-VII, in a panel of human hematopoietic cell lines. FucT-VII was expressed in all E-selectin binding cell lines except one, whereas FucT-IV was expressed by nearly all cell lines, regardless of their ability to bind E- selectin. In addition, transfection of cells with cDNA encoding FucT- VII conferred E-selectin binding ability. Taken together, these data suggest that, regardless of surface carbohydrate phenotype, E-selectin binding ability is determined largely by expression of FucT-VII.     

Eosinophils do respond to fMLP

Eosinophils were isolated from normal human blood by separation over Percoll gradients, which resulted in eosinophil suspensions of a purity higher than 95% and recoveries of about 65%. Normal human eosinophils were found to respond to formyl-methionyl-leucyl-phenylalanine (fMLP) at concentrations greater than 10(-7) mol/L with an increase in the concentration of intracellular free calcium, oxygen consumption, nitroblue tetrazolium reduction, and chemiluminescence. The maximal response of eosinophils to fMLP was lower than that of neutrophils isolated from the same blood samples and required at least ten times as much fMLP as was needed for neutrophils. Low fMLP concentrations (approximately 10(-8) mol/L), which in themselves did not stimulate O2 consumption by either eosinophils or neutrophils, primed these cells to respond to a suboptimal concentration of another stimulus. Purification of eosinophils after treatment of whole blood with fMLP showed that these eosinophils had lost their ability to respond to fMLP. We conclude that normal eosinophils do respond to fMLP and that therefore fMLP should not be used to isolate eosinophils.     

Purification and characterization of a human T-lymphocyte-derived granulocyte-macrophage colony-stimulating factor

We have examined the biologic and physical properties of a human T- lymphocyte granulocyte-macrophage colony-stimulating factor (CSF). The source of the factor is a T-lymphoblast cell line (Mo) that was derived from a patient with a T-cell variant of hairy-cell leukemia. The Mo line constitutively produces a number of lymphokines that are normally produced by mitogen-stimulated T lymphocytes. Medium conditioned by Mo cells grown in the absence of serum is especially rich in CSF activity, and using this source we have purified the CSF to a specific activity of about 3.5 x 10(6) colonies per 10(5) Ficoll-Hypaque-separated human bone marrow cells plated per mg protein. The Mo CSF stimulates the formation of both granulocyte and macrophage colonies in vitro (in about equal numbers) and it has a relatively steep dose-response curve. Both the crude and purified preparations stimulated the formation of eosinophil as well as neutrophil colonies; it is unclear whether this is due to the presence of multiple factors with similar physical properties or a single factor with multiple activities. The CSF has little stimulating activity for mouse bone marrow progenitors. Physically, the Mo CSF is an acidic glycoprotein of molecular weight about 34,000. It binds to concanavalin A-Sepharose, is unusually resistant to denaturing agents and heat treatment, and is not inactivated in the presence of sulfhydryl reagents. The Mo CSF is distinct from factors stimulating erythroid colony formation and inhibiting neutrophil migration that are also produced by Mo cells. It differs in several physical and biologic properties from other human CSFs that have been characterized.