Search PubMed⌕ Search

Biomedical subjects

H Thompson

Publications and source records attributed to H Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1994

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult↗
PubMed1994

Adenocarcinoma arising in an oesophageal colonic interposition graft.

This case report describes the rare complication of an adenocarcinoma developing in a colonic interposition graft 20 years following surgical resection of a postcricoid squamous carcinoma. A free jejunal graft was used for further oesophageal reconstruction following resection of the colonic graft.

Adenocarcinoma↗
PubMed1994

Activity of triphenylselenonium chloride in mammary cancer prevention.

The present study was designed to evaluate the tolerance and cancer chemopreventive activity of triphenylselenonium chloride in female Sprague-Dawley rats. No information is available in the literature on the anticarcinogenic efficacy of a lipophilic cationic selenium compound as exemplified by the triphenylselenonium ion. A short-term preliminary study indicated that it was well tolerated via the dietary route. Supplementation at levels up to 200 p.p.m. Se did not produce any apparent adverse effect in the animals. In the dimethylbenzanthracene mammary cancer model, a level of 30 p.p.m. Se in the diet reduced the total tumor yield by approximately 70% when treatment was applied during either the initiation phase or the post-initiation phase. In the MNU mammary cancer model, the inhibitory response was expressed only during the post-initiation phase. These findings suggest that the triphenylselenonium ion may have multiple modes of action in suppressing the development of neoplasia. Tissue analysis confirmed that there was minimal accumulation of total selenium until the level of supplementation reached 100 p.p.m. Se or above. Our study therefore convincingly demonstrates that triphenylselenonium chloride fits the criteria of an effective and desirable anticancer agent with a distinct separation between the chemopreventive dose range and the toxic dose range.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Comparative effect of inorganic and organic selenocyanate derivatives in mammary cancer chemoprevention.

Recently El-Bayoumy and coworkers have reported that 1,4-phenylene-bis(methylene)selenocyanate (p-XSC) was very effective in inhibiting 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis and adduct formation during the initiation phase (Cancer Res., 52, 2402-2407, 1992). Furthermore, this compound was found to be well tolerated by rats at high doses. The present study was designed to extend these earlier observations by investigating the response to lower levels of p-XSC given either before or after DMBA administration. At a level of 15 p.p.m. Se, p-XSC suppressed total mammary tumor yield by 80% and 52% in the initiation phase and post-initiation phase, respectively. A dose-response effect was evident in the range 5-15 p.p.m. Se. When p-XSC was given at a level of 5 p.p.m. Se during the entire course of the experimental period, total tumor yield was reduced by half. This dose is about 4 x less than the maximum tolerable dose (MTD). Other selenocyanate analogs were also examined in an attempt to obtain information on their respective chemopreventive index, which is calculated as the ratio of MTD to the effective dose which produces approximately a 50% inhibition in total tumor yield (ED50). The reagents studied included potassium selenocyanate, methyl selenocyanate and benzyl selenocyanate, as well as sodium selenite (reference compound). Compared to p-XSC, which has a chemopreventive index of 4.0, the other four compounds have a lower index ranging from 1.3 for sodium selenite and potassium selenocyanate to 2.0 for methyl selenocyanate and 2.5 for benzyl selenocyanate. A high chemopreventive index signifies that a compound is well tolerated at doses required for cancer suppression. The last component of the present study involved the repletion assay of liver glutathione peroxidase in selenium-deficient rats as a biomarker to estimate the metabolizability of the above selenium compounds. The bioavailability data suggest that the selenium from p-XSC is not as efficiently incorporated into glutathione peroxidase as the selenium from selenite or the other selenocyanate analogs. Currently, we are working under the hypothesis that the chemical structure of the RSeCN compound could affect activity per se and also influence the rate of release of selenium from the parent compound, thereby impacting on the anticarcinogenic efficacy, tolerance and bioavailability of the compound.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa.

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.

Adenocarcinoma↗
PubMed1994

Polysulfone capillary fiber for intraocular drug delivery: in vitro and in vivo evaluations.

Studies were conducted to investigate the usefulness of polysulfone capillary fiber (PCF) as a drug delivery device for intraocular applications. Carboxyfluorescein (CF) was used as a model drug to prepare PCF-dye devices for both in vitro and in vivo kinetic studies. For the in vitro study, PCF-CF devices were incubated in 0.1 M phosphate buffer, pH 7.4 at 37 degrees C, and CF release was quantified at various times up to 5 weeks. In vitro results indicated a bi-phasic, sustained-release profile of CF from the PCF device for over 30 days. PCF-CF devices released 5% and 10% of their initial CF contents by the first and second day following incubation, respectively. By 10 days after incubation, approximately 50% of the dye content was released from the PCF-CF devices. The rate of dye release decreased thereafter, such that 65% and 90% of CF was released by 17 and 28 days after incubation, respectively. In a subsequent study, the in vivo kinetics of the PCF-CF device were determined in the rabbit eye. PCF-dye devices were prepared with the following CF formulations: 1) microsphere-incorporated CF; 2) lyophilized liposome-encapsulated CF; or 3) micronized CF powder. A PCF-dye device was implanted in the vitreous cavity, and fluorophotometry from the retina to the anterior chamber was performed at various times up to 45 days to quantify fluorescein level. At the conclusion of the study, eyes were enucleated and examined for histopathology. The time-course study showed fluorescein level for up to 45 days in the vitreous. The midvitreous concentration-time profile indicated a CF t1/2 of 10 and 30 days for the PCF-CF powder and PCF-CF liposome preparation, respectively. In contrast, the PCF device prepared with microsphere-incorporated CF showed fluorescein level with a t1/2 of less than one week in the vitreous. Histological examination of the eyes implanted with PCF or PCF-dye device showed no sign of ocular toxicity. Collectively, these results indicated that the PCF device is biocompatible and may be useful for the extended release of drugs in the posterior segment of the eye.

Analysis of Variance↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗