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Biomedical subjects

H Thompson

Publications and source records attributed to H Thompson.

At least 37 records · Page 2Linked to original sources

Mucosal morphology, cell proliferation and faecal bacteriology in acute pouchitis.

A study was performed to investigate whether acute reservoir ileitis (pouchitis) is associated with specific changes in mucosal morphology, crypt cell kinetics and faecal bacteriology in the ileal pouch. Forty-six patients were studied (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month with metronidazole 400 mg three times daily. An index of villus atrophy and crypt cell production rate (CCPR) were determined in all biopsy material. Faecal bacteriology was assessed in 12 patients with a pouch before and after metronidazole therapy. The mucosa of patients with pouchitis was associated with a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher grade of acute inflammation than that in those without pouchitis. There was no difference in faecal bacterial counts between patients with and without pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P < 0.001), but not with faecal bacteriology. Following metronidazole therapy there was resolution of acute pouch inflammation, increased villus atrophy index (P = 0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts apart from Bacteroides species. These data show that metronidazole therapy does not specifically alter the growth of common faecal bacteria in patients with pouchitis, apart from Bacteroides species. However, metronidazole causes resolution of the typical changes in pouch mucosal morphology and crypt cell kinetics associated with pouchitis.

Adult

Evaluation of the inflammatory infiltrate in pouchitis with 111In-labeled granulocytes.

BACKGROUND: The aim of this study was to elucidate the inflammatory infiltrate in pouchitis and define the changes following metronidazole therapy. METHODS: Twenty-seven patients underwent functional grading, sigmoidoscopic and histological scoring, 111In-labeled granulocyte scanning, and 4-day fecal collections for 111In-labeled granulocyte excretion. Six of the patients with pouchitis underwent repeat studies after 1-month treatment with metronidazole, 400 mg three times daily. RESULTS: The grade of macroscopic inflammation in the pouch mucosa (sigmoidoscopic score) correlated well with the acute histological score (P < 0.0001), chronic histological score (P < 0.001), 4-hour 111In scan (P < 0.001), 24-hour 111In scan (P < 0.001), and with 4-day fecal 111In excretion (P < 0.001). After metronidazole therapy there was decreased inflammatory grade sigmoidoscopically and histologically on the 4- and 24-hour scans and decreased 4-day fecal 111In granulocyte excretion. CONCLUSIONS: This study confirms that the inflammatory infiltrate in pouchitis is acute or chronic, is characterized by neutrophils, is usually localized to pouch mucosa, and is always decreased after metronidazole therapy.

Acute Disease

Haemodialysis recirculation detected by the three-sample method is an artefact.

The efficiency of haemodialysis may be limited by recirculation of blood between venous and arterial needles. Recirculation can be detected directly using a saline dilution method but is most commonly calculated from the urea concentrations of simultaneous samples from venous and arterial lines and a peripheral vein (three-sample method). The methods detect markedly different rates of recirculation in similar study populations. To investigate the possibility that the methods detect different phenomena, we performed both tests on 16 haemodialysis patients at various extracorporeal blood flow rates (Qb). The saline dilution method showed no recirculation in any of the patients, whereas the three-sample method indicated recirculation in all patients. The three-sample method indicated a mean recirculation fraction of 12.5% (SD 6.1) and was not influenced by changing Qb, suggesting that it was not detecting fistula recirculation. The three-sample method detects a solute concentration difference between arterial blood and peripheral blood during dialysis. There appears to be a disequilibrium between a central pool, represented by the arterial sample, and a poorly perfused peripheral pool, relatively isolated from the dialysis process, represented by the peripheral venous sample. The three-sample method for detecting recirculation should be abandoned.

Arteries

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Animals

Outcome of restorative proctocolectomy when the diagnosis is suggestive of Crohn's disease.

Twenty of 81 patients treated by restorative proctocolectomy for presumed ulcerative colitis had some features of Crohn's disease: 10 were classified as definite Crohn's disease and 10 as indeterminate colitis. These pathological features were first apparent during synchronous colectomy and pouch construction in 10 of 11 cases. In the remainder, histological features of possible Crohn's disease were first identified during rectal excision (n = 6), preliminary subtotal colectomy (n = 2), and after pouch excision (= 2). Complications were marginally more common in patients with features of possible Crohn's disease: pelvic sepsis 30% (Crohn's disease 30%, indeterminate colitis 30%) v 20%, fistulas 45% (Crohn's disease 30%, indeterminate colitis 60%) v 16%; ileal stenosis 40% (Crohn's disease 40%, indeterminate colitis 40%) v 21%, pouchitis 50% (Crohn's disease 50%, indeterminate colitis 50%) v 26%, and small bowel obstruction 25% (Crohn's disease 30%, indeterminate colitis 30%) v 13%. Pouch excision or a persistent proximal stoma has been necessary in six patients with possible Crohn's disease (30%) (Crohn's disease 3 cases 30%, indeterminate colitis 3 cases 30%) compared with nine (15%) of the remainder. Median hospital stay, however, was the same and stool frequency in those with a functioning pouch were comparable. These results show that there is a higher complication rate if there are features of Crohn's disease but that the medium term functional results are acceptable if the pouch can be retained.

Adolescent

DNA ploidy in early gastric carcinoma (T1): a flow cytometric study of 100 European cases.

DNA ploidy of 100 early gastric carcinomas (T1) was analysed by flow cytometry on archival material from five European centres and was correlated to morphological features and clinical behaviour. Tumours were classified according to the macroscopic appearance, histological type, and growth pattern. Aneuploidy was observed in 39% of tumours. Aneuploidy was more frequent in submucosal than in mucosal tumours (p = 0.04), in raised than in flat or ulcerated lesions (p = 0.001), and in the intestinal histological than in the diffuse types (p = 0.016). The presence of lymph node metastasis in 10 cases had no obvious relation to DNA ploidy. Five related deaths occurred during the follow up (6 months--16 years) of 84 patients. These results are similar to those reported in a large Japanese series suggesting no major differences between the two populations. Although follow up data were insufficient to relate DNA ploidy to tumour behaviour in this study, the Japanese experience shows that particular attention should be paid to early direction and complete surgical excision of raised intestinal type T1 carcinomas that have a Pen A growth pattern and are aneuploid.

Adult

A pathophysiologic study of diversion proctitis.

Diversion proctitis occurs with variable frequency after exclusion of the fecal stream. Its importance lies in the inability to differentiate it from other types of proctitis that may result in inappropriate therapy and a reluctance to recommend stoma closure. The effect of fecal diversion (n = 18) and restoration of intestinal continuity (n = 10) on human rectal mucosa in patients without inflammatory intestinal disease has been prospectively evaluated. Fecal diversion was associated with macroscopic inflammation in 55 percent of the patients and histologic inflammation in 72 percent, with a variable incidence of aphthoid ulceration, crypt abscess formation and submucosal nodularity. Restoration of continuity was associated with improvement in histologic features in all patients, but the mucosa returned to normal in only 50 percent of the patients. Onset or resolution of diversion proctitis was not associated with any significant changes in colonic cellular proliferation, glycoprotein synthesis or mucosa-associated or luminal flora. The only diagnostic feature of defunctioned proctitis remains its resolution on reintroducing the fecal stream.

Diagnosis, Differential

Distemper encephalitis in pups after vaccination of the dam.

A five-year-old labrador bitch which had whelped 10 pups three days previously was given booster vaccination against distemper, adenovirus, parvovirus, parainfluenzavirus and leptospirosis. Eighteen days later, signs of central nervous system disease developed in some of the pups, five of which were ultimately euthanased. The cause of the nervous disease was found to be canine distemper, and serological studies showed that the infection was limited to some members of the litter, suggesting that the vaccinal rather than a field virus was more likely to have been responsible.

Animals

Construction and characterisation of a yeast artificial chromosome library containing three haploid maize genome equivalents.

We have constructed a yeast artificial chromosome (YAC) library using high-molecular-weight DNA prepared from agarose-embedded leaf protoplasts of the maize inbred line UE95. This library contains 79,000 clones with an average insert size of 145 kb and should therefore represent approximately three haploid genome equivalents. The library is organised as an ordered array in duplicate microtitre plates. Forty-one pools of DNA from 1920 individual clones have been prepared for rapid screening of the library by the polymerase chain reaction (PCR). Using this approach, together with conventional colony hybridisation, we have been able to identify between one and eight positive clones for every probe used.

Chloroplasts

Clinical and pathological findings in feline immunodeficiency virus experimental infection.

A study is described of the clinical and pathological findings in 20 specific pathogen free cats infected when 1 year old with feline immunodeficiency virus and monitored over 12 months. Cats were divided into two groups (A and B). The clinical and clinicopathological features were studied in Group A. In Group B, at 1, 2, 4, 9 and 12 months post infection two cats were necropsied. Clinically all cats developed generalised lymphadenopathy, six cats were neutropenic and five cats lymphopenic. Three cats became febrile with conjunctivitis and anterior uveitis and one of these cats ultimately developed jaundice. Postmortem examinations confirmed a generalised lymphadenopathy involving peripheral and visceral lymph nodes with concurrent stimulation of splenic white matter and mucosal lymphoid tissue of the digestive tract and conjunctiva. Within the lymph nodes there was a reactive follicular hyperplasia accompanied by a paracortical hyperplasia with an increased paracortical vascularity. Unusual features were the presence of lymphoid follicles in the bone marrow, thymus and parathyroid tissue. In addition, aggregates of lymphoid cells were found within salivary glands, kidneys, sclera and choroid of the eye. One cat developed a lymphosarcoma affecting the liver and kidneys at 36 weeks post infection. The cat with jaundice had a cholangitis with marked biliary epithelial hyperplasia.

Animals

Histological and cytological diagnosis of carcinoma of the oesophagus.

Endoscopic examination of the oesophagus accompanied by histological examination of biopsies or cytological examination of smears enables a confident diagnosis of carcinoma to be established within a period of 24-48 h and in the case of cytology within 15-60 min. Squamous cell carcinoma and adenocarcinoma are easily identified in biopsies or smears taken directly from the lesion. The histopathologist should be alerted to the possible diagnosis of Barrett's adenocarcinoma provided adequate information is given regarding the level of the squamo-columnar junction and the level of the targeted lesion. Unusual tumours are encountered rarely and they include carcinosarcoma, mucoepidermoid carcinoma, adenocystic carcinoma, carcinoid, malignant melanoma, oat cell carcinoma, spindle cell sarcoma, malignant lymphoma, Kaposi's sarcoma, etc. Special stains and multiple levels from the biopsies will be required for accurate identification of these tumours. Dysplasia constitutes a difficult diagnostic problem with reference to its significance regarding surveillance and treatment. Low grade dysplasia represents a recommendation for surveillance provided that the patient is regarded as a good surgical risk if cancer should develop at a later stage. High grade dysplasia is associated with a high risk of invasive cancer and close surveillance is required for the detection and treatment of invasive cancer provided also that the patient is a good surgical risk.

Biopsy

Dietary calcium does not reduce experimental colorectal carcinogenesis after small bowel resection despite reducing cellular proliferation.

It has been proposed that colorectal carcinogenesis is accompanied by increased mucosal cell proliferation and that the converse may also apply. To examine this thesis, the crypt cell production rate (CCPR) was measured in eight groups of rats (n = 187) that had received 1,2 dimethylhydrazine, 70% small bowel resection, supplemental dietary calcium, or a combination of these. Analysis of variance showed the following: (1) the CCPR decreased between the ileum and distal colon; (2) the CCPR decreased between 16 and 32 weeks; (3) 1,2 dimethylhydrazine and small bowel resection increased the CCPR and calcium decreased the CCPR independently of one another; (4) the CCPR interacted with 1,2 dimethylhydrazine x small bowel resection, calcium x 1,2 dimethylhydrazine and interacted between the site of bowel and calcium, 1,2 dimethylhydrazine, small bowel resection, and 1,2 dimethylhydrazine x small bowel resection (p = 0.014 to p < 0.001). The tumour yield was reduced by calcium in 1,2 dimethylhydrazine treated animals (chi 2 = 14.1, df = 3, p < 0.01) but was unaffected by calcium in 1,2 dimethylhydrazine and small bowel resection treated animals despite significant differences in the CCPR. An increase of the CCPR both preceded and accompanied colorectal carcinogenesis but reduction of the CCPR was not invariably accompanied by reduced carcinogenes.

1,2-Dimethylhydrazine

Action potential response of the corneal nerves to irritants.

The cornea, in addition to its refractive function for the eye, and by way of its very dense sensory innervation, serves a very important protective function for the visual organ. The cornea receives mainly sensory innervation from the first division of the trigeminal ganglion and a sparse amount of sympathetic fibers. The sensory nerves carry out their protective function by responding to various types of stimuli in a way so that they are all perceived psychologically as painful. Neurophysiological data indicates that, despite the morphological similarity of free-nerve endings in the cornea, they are differentiated functionally. A concentration series, (0.005 to 10% solution in saline), of various potential irritants (phosphate detergent, baby shampoo, liquid chlorine bleach, herbal shampoo, onion juice, SDS, and sodium chloride) was applied directly to the cornea of the anesthetized rabbit. Neural activity was assessed from extra-cellular records of long ciliary nerve over a ten second application period, and for ten seconds following stimulus removal. Baby shampoo was non-stimulatory over the applied concentration range. Sodium chloride, on the other hand, exhibited linear response dynamics over the range of 0.01 to 5% (p < 0.001). SDS was highly stimulatory, but showed no predictable concentration or response relationship. All of the other irritants tested responded in a logarithmic fashion. This suggests that the application of neurophysiological techniques to assess the pain and potential inflammatory aspects of a substance for human use can be monitored in this fashion. Moreover, response profiles for various classes of compounds and homologous series, as well as pH and osmolality, can be established.

Action Potentials

Labor in the gravida with 10 or more years between pregnancies.

It has been suggested that women who have had a pregnancy interval of 10 or more years would have prolonged labor in pregnancies after the first, as do primigravidas. In a series of 94 multiparas with 10 or more years between pregnancies and 63 age-matched, multiparous controls, there was no significant difference in the length of the latent phase of labor or of the first, second and third stages of active labor in the two groups. The concept of a "physiologic primigravida" in these cases should be abandoned.

Adult