A randomized trial of antihuman thymocyte globulin versus murine monoclonal antihuman T-cell antibodies as immunosuppressive therapy for aplastic anemia.

A prospective randomized trial was undertaken to compare the efficacy and toxicity of murine antihunman T-cell monoclonal antibody (mcAb) therapy to that of horse antihuman thymocyte globulin (ATG) in the treatment of severe aplastic anemia (AA). Patients were randomized into one of the two treatment groups as well as to receive or not receive androgens. Median duration of aplasia prior to treatment was 1.

Designing phase II studies in the context of a programme of clinical research.

Conventional statistical determinations of sample size in phase II studies typically lead to sample sizes of the order of 25 (Schoenfeld, 1980, International Journal of Radiation Oncology, Biology and Physics 6, 371-374). When the development of new treatments is proceeding rapidly relative to the recruitment of suitable patients, such requirements can prove to be too demanding. As a result, either sample sizes are reduced by a rather arbitrary weakening of the risk specifications, or certain new treatments go untested.

A FORTRAN program for the design and analysis of sequential clinical trials.

Clinical scientists are becoming increasingly aware of the need to monitor clinical trials in progress, and to validate their procedure by the use of a formal sequential design. An interactive program, written in FORTRAN 77 and called "PEST: Planning and Evaluation of Sequential Tests," is introduced. The program can be used to design trials based on the sequential probability ratio test, the triangular test, and the restricted procedure, among others.

Pulmonary bronchoalveolar cell and protein kinetics in dogs given total-body irradiation, autologous marrow grafts, and methotrexate.

Patients receiving allogeneic marrow transplantation for hematologic malignancies commonly are conditioned with total body irradiation (TBI) and given methotrexate (MTX) in an attempt to prevent graft-versus-host disease. To study the effects of TBI with or without MTX on bronchoalveolar cells and proteins, we performed sequential bronchoalveolar lavages in dogs before and after irradiation. Ten dogs received 9 Gy TBI followed by autologous marrow grafts.

An outbreak of Mycobacterium bovis infection in cats in an animal house.

An outbreak of tuberculosis due to Mycobacterium bovis in cats in an animal house was investigated. It was concluded that the index case was infected by ingestion of contaminated meat obtained from a knackery and that some of the other cases were infected by inhalation of tubercle bacilli shed from a discharging sinus in the index case. A possum was also infected and a research worker apparently received a significant challenge.

Alterations in membrane sugars during epidermal differentiation: visualization with lectins and role of glycosidases.

Differentiation in keratinizing epithelia involves the orderly transformation of basal germinal cells into an exterior cornified layer. We have employed rhodamine-conjugated lectins to visualize distinctive changes in the localization of keratinocyte membrane glycoconjugates during epidermal differentiation. The dermis, basement membrane, and epidermal cell membranes stained positively for mannose, alpha- and beta-galactose, N-acetyl-glucosamine, and sialic acid.

The analysis of a sequential clinical trial for the comparison of two lung cancer treatments.

Methods adopted in the analysis of data from a randomized controlled trial of a new treatment for inoperable lung cancer are described. The trial design employed the sequential logrank test using length of survival from time of randomization as the principal outcome measure. We describe the practical arrangements for regular inspections of the accumulating data as required by the sequential design, and also for more extensive but less formal interim analyses, and present some of the results.

Isolation of benzimidazole resistant strains of Ostertagia circumcincta from British sheep.

Two strains of Ostertagia circumcincta were isolated from sheep in Great Britain; one (CVL strain) from a breeding flock maintained at the Central Veterinary Laboratory, the other (H2 strain) from a commercial flock in southern England. Their resistance to benzimidazole anthelmintics was assessed by means of in vitro egg hatch assays and slaughter trials. In vitro egg hatch assays gave calculated ED50 estimates of 0.

Group sequential clinical trials with triangular continuation regions.

In this paper a new class of group sequential procedures for clinical trials is introduced, and the use of these procedures is illustrated by reference to a recently completed comparative study. In a group sequential trial the decision to stop or to continue is made at regular intervals throughout the trial, but not as frequently as after every patient response. This more practical formulation retains most of the advantages of sequential analysis, particularly the economy in sample size.

Muscarinic acetylcholine receptors of the small intestine and pancreas of the rat: distribution and the effect of vagotomy.

1. The distribution of muscarinic cholinergic receptors (mAChR), detected by atropine-inhibitable binding of [3H] quinuclidinyl benzilate, was examined in membrane fractions of pancreas, small intestinal muscle, mucosa, villi and crypts of sham-operated and vagotomized rats. 2.

The design of a sequential clinical trial for the comparison of two lung cancer treatments.

The steps in designing a controlled trial to evaluate a new treatment for inoperable carcinoma of the bronchus are described. The principal outcome measure is survival time from treatment allocation, and the duration of the trial is determined by application of the sequential logrank test. The detailed determination of the stopping rule and the arrangements for analyses are described.

Congenital rubella affecting an infant whose mother had rubella antibodies before conception.

A woman who had had high titres of rubella antibodies some months before she became pregnant gave birth to an infant in whom congenital rubella was confirmed at 4 months. Rubella haemagglutination inhibition tests, complement fixation tests, and immunofluorescence tests with anti-human IgG were carried out on sera from the mother. Rubella antibody titres in sera obtained in March 1971, seven and a half months before conception, were equivalent to 400 units, which is usually taken as indicating good immunity.

Radiological articular involvement in the dominant hand in rheumatoid arthritis.

Scoring the severity of joint involvement in the x-rays of hands of patients with rheumatoid arthritis showed significantly greater joint destruction in the dominant hand. The difference was seen in all the joints, and especially in the wrists, but with the exception of the metacarpophalangeal joint of the thumb. The grip strength was not, however, different in the 2 hands.

Interaction of Escherichia coli K88 antigen with porcine intestinal brush border membranes.

The fimbria-associated Escherichia coli antigen, K88, was purified to homogeneity as determined by polyacrylamide gel electrophoresis and immunodiffusion. This polymeric antigen consists of noncovalently linked subunits, containing little or no carbohydrate, and has a monomeric molecular weight of 23,000. When a binding assay employing differential filtration was used, K88 formed complexes with isolated porcine intestinal brush border membranes.

Quantitative electrophysiological study of alcoholic neuropathy.

Thirty-one chronic alcoholic patients were investigated using quantitative electrophysiological techniques. Estimates of the numbers of functioning motor units in the extensor digitorum brevis muscles and measurements of the parameters of the potentials of these units are presented along with the values for motor nerve conduction velocities in the innervating lateral popliteal nerves. Motor conduction velocities and sensory nerve action potential amplitudes were also measured in the ulnar nerves.

Effects of sodium butyrate and dimethylsulfoxide on biochemical properties of human colon cancer cells.

Sodium butyrate and dimethylsulfoxide (DMSO) have marked effects on the growth, morphology, and biochemistry of two human colonic adenocarcinoma cell lines in culture. Doubling times were increased between 18% and 660% while cell viability was unaffected. Both cell lines formed colonies in soft agar in the absence of butyrate of DMSO, but no colonies were observed in the presence of these agents.

An inhibitor of lymphocyte proliferation produced by a human colonic adenocarcinoma cell line in culture.

The culture fluid taken from a human colonic adenocarcinoma cell line, SKCO-1, inhibited mitogenic stimulation of mouse lymphocytes measured by reductions in blast information or [3H]thymidine uptake. The inhibitor was not cytotoxic to lymphocytes nor did it alter the growth rates of 21 other cell lines examined. However, the in vitro growth rates of two murine lymphoid tumor lines were also markedly reduced by the SKCO-1 medium.