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Biomedical subjects

A Ferguson

Publications and source records attributed to A Ferguson.

At least 289 records · Page 16Linked to original sources
PubMed1978

Chemotherapy of small cell carcinoma of the lung with V.P. 16-213.

A Phase II study of V.P. 16-213 administered to 47 patients suffering from small cell carcinoma of the bronchus. V.P. 16-213 was given as an intravenous infusion over 15 minutes daily for five consecutive days using 60 mg/m2/d at 14-day intervals. Oral V.P. in 100 mg doses was given twice a week between the intravenous courses. Objective response rate for this drug compared favourably with that of other single agents reported. All but two patients showed a degree of response to treatment and 24 of 47 patients showed a true objective response to treatment. The overall median survival of these patients was 225 days and localized disease 278 days. The quality of survival was such that responders lived relatively normal lives up to the latter stages of their disease. The majority of patients had a marked response in performance status, 37 out of 47 showing an improvement. Three patients are alive and well at more than 27 months. In all cases the side effects were minimal. Alopecia was common and reversible haematological complications occurred. Severe toxicity was not encountered and the drug was well tolerated with supportive antiemetic therapy at onset of treatment.

Bone Marrow↗
PubMed1978

Hypersensitivity reactions in the small intestine. IV. Influence of allograft rejection on small intestinal mucosal architecture: a scanning and transmission electron microscope study.

The effect of a local delayed hypersensitivity reaction (allograft rejection) on small intestinal architecture has been examined by using scanning electron microscopy of the mucosal surface. In isografts, regarded as a morphological basis for normality of the system, the villi appeared normal and finger like. In allografts the appearances ranged from fairly normal areas to others with stunted and ridged villi, and flat areas in which crypt mouths opened on to the flat mucosal surface. The fine structure of epithelial cells was studied further by transmission electron microscopy. There was an apparent reduction in the size of the microvillous border in allografts but no other consistent abnormality. The similarities between this model of allograft rejection, and untreated coeliac disease in man, are highlighted and contrasted with the effects of acute radiation injury on the intestine.

Animals↗
PubMed1978

The effects of different component response requirements in multiple and concurrent schedules.

Six pigeons were trained on multiple and concurrent schedules. The reinforcement rates were varied systematically (a) when lever pressing was required in one component and key pecking in the successive component; (b) when lever pressing was required in both multiple components; (c) when key pecking was required in both multiple components; and (d) when key pecking was required on one schedule and lever pressing was required on the concurrently-available schedule. Only the absolute level of responding was changed by different response requirements. Analyzed by the generalized matching law, performance under different response requirements resulted in a bias toward key pecking, and the measured response bias was the same in multiple and concurrent schedule arrangements. The bias in time measures obtained from concurrent schedule performance was reliably smaller than the obtained response biases. The sensitivity to reinforcement-rate changes was ordered: concurrent key-lever; multiple key-key; multiple lever-key; and, the least sensitive, multiple lever-lever. The results confirm that requirements of different topographical responses can be handled by the generalized matching law mainly in the bias parameter, but problems for this type of analysis may be caused by the changing sensitivity to reinforcement in multiple schedule performance as response requirements are changed.

Journal Article↗
PubMed1978

Small intestinal epithelial cell kinetics and protozoal infection in mice.

The effects of chronic protozoal infection on small intestinal architecture have been examined in mice, infected with Giardia muris and Hexamita muris. Techniques used were conventional histology, quantitation of intraepithelial lymphocytes, microdissection and measurement of individual villi and crypts, and epithelial cell kinetic studies. The histology of small intestine from infected mice appeared normal apart from the intraepithelial lymphocyte numbers. Mean intraepithelial lymphocyte counts in two groups of uninfected mice were 11.6 and 13.6 per 100 epithelial cells, and in two groups of infected mice were 17.6 and 21.8. Dynamic studies showed that protozoal infection doubled the cell production per crypt per hour from mean values of 6.2, 7.3, and 8.2 in three groups of uninfected animals, to 11.8, 13.4, and 17.1 in groups of chronically infected mice. Cell production per villus was also influenced by protozoal infection, with values of 93, 99, and 101 cells per hr in groups of uninfected animals whereas in infected mice the values were 155, 162, and 180 cells per hr. Although there was no reduction in villus height in the infected animals, radioautography using [3H]thymidine confirmed that the enterocytes moved rapidly up the sides of the villi than was the case for uninfected mice.

Animals↗
PubMed1977

Technique for microdissection and measurement in biopsies of human small intestine.

A microdissection and measurement technique has been adapted for biopsy of human small intestine. Specimens fixed in alcohol and acetic acid are Schiff stained in bulk. Villi and crypts are then dissected out under a dissecting microscope, placed under a coverslip, examined, measured, and the number of mitoses in individual crypts counted. With this method specimens of normal small intestine have been found to have villi 500 microns to 1100 microns long and crypts 150 microns to 300 microns. These values were double those obtained when measuring sections of the same specimens stained with haematoxylin and eosin. The mean number of mitoses per crypt in normal duodenum and jejunum ranged from 1 to 12 and most of the cells in mitosis were in prophase or telophase. This rapid, sensitive, and inexpensive technique complements the available methods of measuring small intestinal architecture.

Biopsy↗
PubMed1977

Hypersensitivity reactions in the small intestine. III. The effects of allograft rejection and of graft-versus-host disease on epithelial cell kinetics.

Allograft rejection of fetal intestine and graft-versus-host (GvH) disease have been used to study the effects of cell-mediated immune reactions on epithelial cell kinetics in mouse small intestine. In heterotopically transplanted isografts the cell production rate per crypt was similar to that in normally sited small intestine of the same age. However there was a six-fold increase in the rate of cell production per crypt during allograft rejection and a three-fold increase during GvH disease. Furthermore animals with GvH disease developed villous atrophy and had fewer crypts per villus that littermate controls. At the age of 19 days cell production per villus per hour was 97-5 in animals with GvH disease compared with 54-6 in controls. These results indicate that the pathological entity of 'partial villous atrophy' evolves in two distinct phases. Phase 1, a state of increased cell turnover with crypt hyperplasia but villi of normal length precedes the development of Phase 2, true villous atrophy.

Animals↗
PubMed1976

Intraepithelial lymphocyte counts in small intestinal biopsies from children with diarrhoea.

We have investigated small intestinal biopsies from children with coeliac disease, acute gastroenteritis, failure to thrive and giardiasis, to find out if a high intraepithelial lymphocyte count is a feature specific to coeliac disease, or whether it is always associated with partial or subtotal villous atrophy. The results indicate that the normal range for childrens' intraepithelial lymphocyte counts is similar to that for adults (around 6-40 lymphocytes per 100 epithelial cells); that counts are high in coeliac disease, but also in some children with giardiasis or with failure to thrive in whom the jejunal biopsy appears otherwise normal; and that intraepithelial lymphocyte counts are normal in acute gastroenteritis even when there is partial villous atrophy with increased lamina propria lymphoid cell infiltrate. Thus, this measurement of small intestinal lymphocyte infiltration may be of diagnostic value is differentiating the diarrhoea of food intolerance from infectious diarrhoeas in young children.

Acute Disease↗
PubMed1976

Hypersensitivity reactions in the small intestine. 2. Effects of allograft rejection on mucosal architecture and lymphoid cell infiltrate.

Small intestinal mucosa contains both thymus dependent and thymus independent lymphoid cells and thus has the capacity to act via humoral and cellular mechanisms as a site of local immunity and local hypersensitivity. Allograft rejection of mouse small intestine is a model of a local cell mediated reaction. The effects of this clearly defined, immunologically mediated damage villi, crypts, enterocytes, and lymphoid cell infiltrate have been assessed by comparing the morphology of rejecting allografts with that of isografts and normal small intestine of the same age. In rejection there is infiltration of the lamina propria with lymphocytes, hyperplasia of the crypts of Lieberkuhn, and an eventual sloughing off of the mucosa. Usually, but not always, there is villous atrophy and increased numbers of intraepithelial lymphocytes. However, the morphology of individual enterocytes remains normal throughout rejection and neither plasma cells nor polymorphonuclear leucocytes infiltrate the lamina propria before mucosal ulceration. These results show unequivocally that a local T cell mediated immune response causes villous atrophy and crypt hyperplasia in this animal model, and since there is no evidence of local enterocyte cytotoxicity, a lymphokine may be the link between the activated T cell and the effects on mucosal architecture. We suggest that a local CMI reaction may be the cause of villous atrophy, crypt hyperplasia, and malabsorption in many clinical and experimental conditions, including coeliac disease, food allergy, and intestinal infections.

Animals↗
PubMed1976

Histopathology of cell mediated immune reaction in mouse colon--allograft rejection.

Grafts of mouse fetal colon, implanted beneath the renal capsule of adult hosts, have been used to study the growth and development of colonic isografts and the rejection of colonic allografts. Isografts grew normally and maintained a structure similar to normal colon. Grafts between strains with H2 histocompatibility differences were rejected by 13 days after transplantation. Early progressive infiltration of the grafts by lymphoid cells was followed by increasing damage to, and subsequent loss of, the epithelial cell layer and destruction of the underlying muscle, changes which parallel those seen in rejection of skin and small bowel. The increase in survival time which is seen in allografts between strains with H2 identity was longer in the colon than has been seen in the skin or small bowel; none of the allografts of colon were completely rejected before 30 days, and some remained viable at 50 days. Comparison of the appearances of rejection in the colon with those of ulcerative colitis and colonic Crohn's disease does not show the striking similarity which is seen between small bowel rejection and coeliac disease. Many of the individual features of these diseases are, however, present in the course of colonic rejection.

Animals↗
PubMed1976

Food antibodies in patients with dermatitis herpetiformis and adult coeliac disease - relationship to jejunal morphology.

Serum antibodies to a variety of dietary proteins were investigated in 26 patients with adult coeliac disease (ACD, 14 untreated and 17 treated with a gluten-free diet) and 38 patients with dermatitis herpetiformis (DH) with varying small bowel abnormalities. The incidence of one or more positive tests was highest in untreated ACD (73.4%) and DH with subtotal villous atrophy (57.4%). This incidence fell with morphological improvement, being 56.4% in treated ACD patients with partial villous atrophy (PVA), and 33.4% in DH with PVA, and 0% in DH with normal biopsies. The height of the serum antibody titre also fell with morphological improvement. These results show that there is an abnormally high incidence of dietary antibodies in patients with DH, and this correlates with the degree of small bowel damage.

Adult↗
PubMed1975

Immune status of children with and without severe infection during remission of malignant disease.

The immune status of children with malignant disease in remission was assessed usingvarious immune function tests. Children with infections had significantlymore neutropenia, hypogammaglobulinaemia, and impaired cell-mediated immune responses than those without. These two groups combined had much more absolute lymphopenia and impairment of both cell-mediated immunity and antibody-producing capacity thancontrol children with non-malignant conditions. Regular immunological evaluation isrecommended for children with malignant disease when new intensive treatment schedules are under trial and for individual patients particularly prone to develop infections during treatment.

Antibody Formation↗
PubMed1975

Cell-mediated immunity to gliadin within the small-intestinal mucosa in coeliac disease.

In an attempt to demonstrate local cell-mediated immunity (C.M.I.) to gliadin in patients with coeliac disease, fragments of jejunal-biopsy specimens were cultured in the presence and absence of alpha-gliadin and the culture-medium was assayed for its capacity to inhibit migration of normal human peripheral-blood leucocytes (i.e., for a migration-inhibition factor [M.I.F.]). No M.I.F. activity was detected in the culture-medium when biopsy specimens from patients with coeliac disease or controls were cultured without added antigen. However, an M.I.F. was secreted into the culture-medium when biopsy specimens from patients with coeliac disease were cultured with alpha-gliadin. These findings suggest that there is a population of lymphocytes which are sensitised to gliadin in the intestinal mucosa of patients with untreated coeliac disease. They support the theory that a local C.M.I. reaction to gliadin may be the cause of villous atrophy and crypt hyperplasia in coeliac disease.

Adult↗