Search PubMed⌕ Search

Biomedical subjects

M J O'Brien

Publications and source records attributed to M J O'Brien.

At least 73 records · Page 4Linked to original sources
PubMed1990

Risk and surveillance of individuals with colorectal polyps. Who Collaborating Centre for the Prevention of Colorectal Cancer.

Since colorectal adenomas are very probably the precursors of colorectal cancer, their detection and removal should result in a decrease in the incidence and mortality from colorectal cancer. Individuals who harbour an adenoma have a 30-50% probability of having additional adenomas at that time, and a 30% probability of having additional adenomas later. Adenomas are prevalent in countries where colorectal cancer is prevalent, about two-thirds of them being tubular and the rest tubulovillous or villous. The initial management of patients with an adenoma consists in searching by colonoscopy the entire colon and removing all additional polyps. Surgical resection is required wherever there is invasive cancer with adverse histological factors. Follow-up in most patients can be after 2-4 years, earlier follow-up being reserved for patients with numerous polyps or with a polyp that had been removed piecemeal. The results of ongoing trials should provide firm guidelines for follow-up and could also be used in mathematical modelling to examine alternative strategies and to help understand the evolving patterns of appearance of new polyps. Finally, a deeper understanding of the biology and inherited and acquired genetics will help identify individuals at risk for adenomas initially and at follow-up. Nutritional factors may also provide a basis for prevention of adenomas in high-risk countries. Many of these issues are being addressed in current research.

Adenoma↗
PubMed1990

A three-dimensional system for long-term culture of human colorectal adenomas.

Studies of the adenoma-carcinoma sequence in the colon and rectum have been limited by the paucity of experimental models of adenoma growth and progression. Progress recently was reported in the development of monolayer culture systems. The principal objective of this study was to develop a primary culture system for colorectal adenomas that would simulate three-dimensional in vivo growth. We used a calcium alginate encapsulation technique that was previously described for established tumor cell lines. Briefly, fresh resected specimens were washed, minced into small multicellular particles called microadenomas, and encapsulated in 1% calcium alginate pellets. The pellets were maintained in minimum essential medium containing 10% fetal bovine serum at 37 degrees C in humidified atmosphere of 95% air, 5% CO2. Ten of eleven adenomas, including six tubular, three tubulovillous, and one villous have been successfully cultured for 34 to 162 days. Cell viability was confirmed histologically by light and electron microscopy. The cells were characterized as epithelial by morphologic features and ultrastructural studies, which showed a high degree of cellular differentiation, including villous brush borders and many desmosomes. Both tubular and villuslike structures have been observed in vitro, correlating in some cases with the histology of the parent adenoma. Measurements of proliferative activity by [3H]thymidine autoradiography or immunohistochemical staining with the monoclonal antibody Ki-67 demonstrated growth fractions of 9% to 25%. A simple, highly efficient primary culture system was developed for the long-term maintenance of adenomas that promotes three-dimensional growth patterns and growth rates analogous to those seen in vivo. This model provides an opportunity to develop an experimental system for longitudinal studies of pathologic and molecular parameters in adenoma progression to carcinoma.

Adenoma↗
PubMed1990

The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.

The National Polyp Study (NPS), a randomized clinical trial to evaluate effective surveillance of patients discovered to have one or more colorectal adenomas, was the framework for this statistical analysis which used a multiple logistic model to assess the independent risk factors of patient and polyp characteristics associated with high-grade dysplasia in adenomas. The database included 3371 adenomas from 1867 patients. Adenoma size and the extent of the villous component were found to be the major independent polyp risk factors associated with high-grade dysplasia (p less than 0.0001). The adjusted odds ratios were 3.3 for medium-sized adenomas and 7.7 for large adenomas relative to small adenomas and 2.7 for villous A adenomas, 3.4 for villous B adenomas, and 8.1 for villous C and D adenomas relative to tubular adenomas. Increased frequency of high-grade dysplasia in adenomas located distal to the splenic flexure was attributable mainly to increased size and villous component rather than to location per se. The adjusted odds ratio was 1.4 (p less than 0.11) for left-sided location. Multiplicity of adenomas affected the risk for high-grade dysplasia in patients but was dependent on adenoma size and villous component and was not an independent factor. The adjusted odds ratio was 1.3 (p less than 0.17) for multiplicity. Increasing age was associated with risk for high-grade dysplasia in patients, and this effect was independent of the effect of adenoma size and histological type. The adjusted odds ratio was 1.8 (p less than 0.0016) for age greater than or equal to 60 yr. Gender was not associated with high-grade dysplasia. The adjusted odds ratio was 1.0 (p less than 0.95) for men. The size of the patient series, the prospective nature of the data collection, the completeness of information on all patients, the requirements of complete examination of the entire colon and pathological examination of all lesions encountered, and the exclusion of patients with previously diagnosed adenomas are, collectively, features unique to this study. The detailed model provided by the analysis integrates multiple patient and adenoma factors associated with high-grade dysplasia in colorectal adenomas.

Adenoma↗
PubMed1989

Normal fetal hemoglobin levels in the sudden infant death syndrome.

It has been reported that infants who die of the sudden infant death syndrome (SIDS) have elevated fetal hemoglobin levels. To test this hypothesis, we determined the level of fetal hemoglobin in dead and living infants in three different laboratories by three methods: high-performance liquid chromatography, polyacrylamide-gel electrophoresis, and cell-based immunofluorescence assays for fetal hemoglobin-containing red cells (F cells). Our infant study population consisted of 67 infants who had died of SIDS, 22 control infants examined at autopsy, and 80 living infants. The fetal hemoglobin level was not higher in the infants who had died of SIDS than in the control infants for any age group analyzed. Immunofluorescence assays for F cells were also performed in blood samples from 105 mothers of infants who had died of SIDS, 55 adult female controls, 52 fathers of infants who had died of SIDS, and 67 adult male controls. The percentage of fetal hemoglobin-containing red cells in the parents of infants who had died of SIDS was not statistically different from that in sex-matched adults in the control groups. We conclude that elevated fetal hemoglobin levels in infants or their parents are not suitable for use as indicators of the risk of SIDS in the infants. Furthermore, the fetal hemoglobin level is not useful as a postmortem marker of an infant's having died of SIDS.

Adult↗
PubMed1989

Immunohistochemical analysis of cell kinetic parameters in colonic adenocarcinomas, adenomas, and normal mucosa.

The monoclonal antibody Ki-67 identifies a nuclear antigen that is expressed in proliferating cells in G1, G2, S, and M phases of the cell cycle. An immunoperoxidase method and this antibody were used to identify proliferating cells in sections of colorectal tissues--normal colon (n = 10), colorectal polyps (n = 20), and adenocarcinoma (n = 28). Colorectal adenomas showed a uniform distribution of positive nuclear staining throughout the sections, including the cells of the adenoma surface, while staining in the normal mucosa was confined to the middle third and lower third of the crypts. Areas of polyps with numerous Ki-67-positive epithelial cells invariably showed immature or dysplastic histology and, conversely, glands that lacked such histologic features had low Ki-67 staining frequency or were negative. In adenomas, nuclei located toward the luminal surface of glands were more likely to be Ki-67-positive than those located basally in the cells. The mean Ki-67 score (a measure of positive staining nuclei) for adenomas was 45.5 compared to a mean score of 66.3 for adenocarcinomas in the carcinomas studied (P less than .001). Ki-67 score did not correlate with histologic grade or Duke's stage. Ki-67 staining can be used to characterize the proliferative characteristics of normal colonic mucosa, adenomas, and carcinomas.

Adenocarcinoma↗
PubMed1988

EEG coherence functions for normal newborns in relation to their sleep state.

While power spectra provide little information about the properties of the newborn EEG, the coherence functions (especially interhemispheric) have a characteristic shape for each of the 2 sleep states. Coherence functions may therefore be clinically more important than spectra. For this reason, baseline data for normal newborns have been produced as a reference against which coherences from patients can be compared. It is stressed that for a sleeping newborn the behavioural state must be known for the coherence function to be interpretable. Furthermore, since intraindividual variability is large, data from long recordings are required. The results are discussed in the light of the existing literature.

Brain↗
PubMed1987

Coherence patterns of the infant sleep EEG in absence of the corpus callosum.

The role of the corpus callosum in the relationship between the EEGs of the two cerebral hemispheres was studied by comparing 3 infants with congenital agenesis of the corpus callosum with a group of neurologically normal infants. Coherence functions were computed for symmetrical pairs of EEG derivations; in the frequency bands below 4 Hz they were in general much lower in the acallosal infants than in the normals.

Agenesis of Corpus Callosum↗
PubMed1987

Transient flattenings in the EEG of newborns--a benign variation.

A report on 43 instances of transient flattening of the EEG in sleeping newborns occurring near the onset of state 1 is presented. The depression of EEG activity is variable and lasts about 1 min. It is followed usually by highly discontinuous activity (tracé discontinu) which fades after a variable time (less than 1.5 min in 75% of cases), into a normal state 1 pattern. The incidence was 24% in a mixed group of infants of 43 weeks CA and under. Bilateral events were twice as common as unilateral ones. Flattenings were only seen at or close to the onset of the first state 1 in a sleep episode. We suspect that the phenomenon reflects the unusual functioning of mechanisms underlying the normal process of change from the low voltage continuous EEG in behavioural state 2 (active or REM sleep) to the higher voltage so-called synchronized discontinuous pattern of state 1 (non-REM or quiet sleep). Flattenings have no clinical significance beyond their importance as a normal variation in the neonatal EEG, about whose existence electroencephalographers should be aware. Post-flattening bursting should not be misinterpreted as epileptic activity.

Child Behavior↗
PubMed1987

Differential effects of Clostridium difficile toxins A and B on rabbit ileum.

The pathogenesis of Clostridium difficile enterocolitis appears to involve colonization of the bowel followed by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. The purpose of this study was to determine the effect of purified toxins A and B on intestinal secretion, epithelial permeability, and morphology in perfused rabbit ileal loops. Intestinal permeability after toxin exposure was assessed by blood-to-lumen clearance of [3H]mannitol. Toxin A at doses of 5-100 micrograms/10 cm ileal loop caused a threefold to fivefold increase in [3H]mannitol permeability (p less than 0.001) vs. equal concentrations of toxin B or buffer control. In addition, perfusate from toxin A-exposed loops contained significantly more neutrophils (p less than 0.001) than toxin B or control loops. Toxin A caused severe epithelial cell necrosis with destruction of villi and polymorphonuclear infiltration. Electron microscopy of mucosa subjected to a low dose of toxin revealed widespread nonspecific dilatation of endoplasmic reticulum and mitochondrial swelling. In contrast to these effects of toxin A in ileal loops, in vitro experiments with ileal explants in short-term organ culture revealed that toxin A had no effect on epithelial cell permeability, protein synthesis, release of alkaline phosphatase, or morphology. Our results show that purified toxin A but not toxin B causes severe inflammatory enteritis in rabbit ileal loops, but has no discernable effect on rabbit ileum in vitro. We speculate that toxin A may contribute significantly to intestinal damage in C. difficile-associated colitis and diarrhea.

Animals↗
PubMed1987

Transcutaneous respiratory electromyographic monitoring.

The integrated diaphragm electromyogram (EMG) signal reflects function from the inspiratory centers to the neuromuscular junction. The feasibility and potential value of transcutaneous diaphragm electromyography (tcEMG) was confirmed in a group of infants using two prototype respiratory EMG monitors. Infants were monitored continuously for periods ranging from hours to days. One hundred were monitored for clinical reasons, looking for disordered respiratory behavior, while 47 were studied for technical/experimental reasons. Reliable measurements of diaphragm EMG activity were obtained, provided fully shielded electrode cables were used. Measurements in 28 ventilated infants and one adult confirmed that, unlike impedance and other non-electrophysiologic measures, tcEMG monitoring is not contaminated by ventilator-induced respiratory movements. The potential value of tcEMG monitoring in ventilated subjects is exemplified by illustrations of: diaphragmatic inactivity from phrenic nerve injury, inadequate central drive, and neuromuscular block; augmented expiratory muscle activity; and progressive increase in inspiratory diaphragmatic activity in the presence of a tension pneumothorax. TcEMG monitoring should prove a worthwhile addition to the available noninvasive respiratory monitoring techniques.

Diaphragm↗
PubMed1987

Ultrastructural differentiation and CEA expression of butyrate-treated human pancreatic carcinoma cells.

The effects of butyrate (a biological response modifier) on cellular morphologic features and carcinoembryonic antigen (CEA) expression of human pancreatic carcinoma cells were studied and compared in a well-differentiated, CEA-producing cell line (CAPAN-1), and a poorly differentiated cell line (PANC-1). Butyrate treatment resulted in the acquisition of phenotypic traits commonly attributed to increased "differentiation," including a twofold increase in doubling time, decreased saturation densities, and approximately 50% reduction in colony forming efficiency in both cell lines. Elongation and flattening of cells with extending cellular processes were seen by light microscopy. Significant ultrastructural changes were seen only in the PANC-1 cells, including an increased number of intercellular desmosomes, tonofilaments, and lipid droplets. In contrast, to the coarsely clumped nuclear chromatin (heterochromatin) of untreated PANC-1 cells, the nuclei of the butyrate-treated cells consisted of finely dispersed chromatin (euchromatin). CAPAN-1 cells responded to butyrate with increased CEA synthesis and release. This effect was greatest in the stationary growth phase. Butyrate had no effect on the already low rate of CEA synthesis by PANC-1 cells. These studies suggest that CEA synthesis and state of differentiation are affected independently by butyrate treatment and that the original tumor phenotype plays an important role in response to such treatment.

Adenocarcinoma↗
PubMed1987

Isolation and characterization of an undifferentiated human colon carcinoma cell line (MIP-101).

An undifferentiated human colon carcinoma cell line was established from tumor tissue obtained from metastasis to the liver of colonic adenocarcinoma in a patient with fulminant Dukes D colorectal carcinoma. Histological analysis of the tumor biopsy from the liver confirmed the hospital pathology report of poorly differentiated colonic adenocarcinoma. Explants of this tumor tissue xenografted into a nude mouse were used to establish an epithelioid-like cell culture line, MIP-101. The cell line formed tumors in nude mice that histologically appeared undifferentiated and did not stain for carcinoembryonic antigen (CEA). No CEA was present either by radioimmunoassay (RIA) of the culture supernatant or by immunoperoxidase staining of the tumors or monolayers. MIP-101 appears to be one of the most undifferentiated human colon carcinoma cells lines available. It should prove useful in the search for markers of undifferentiated colonic cancer and in studies of colonic cancer differentiation.

Adenocarcinoma↗
PubMed1987

Diversion colitis. Pathologic findings in a resected sigmoid colon and rectum.

We present here the detailed pathologic findings in the resected colon and rectum from a paraplegic patient with severely symptomatic diversion colitis and lack of anorectal function. Previous reports of the pathology of this condition have been confined to biopsy findings. A diffuse nodularity caused by lymphoid hyperplasia and an inflammatory process confined to the colorectal mucosa with erosions, crypt abscesses, mucin granulomas, and aphthoid ulcers were the main features. There was minimal distortion of crypt architecture. The pathologic features of this entity are compared to those of other inflammatory disorders of the colon and rectum.

Adult↗
PubMed1986

Cholecystitis secondary to infusion chemotherapy.

This report centers on a patient with metastatic colorectal cancer who developed acute and chronic cholecystitis secondary to the infusion of FUDR (fluoro-deoxyuridine) into the hepatic artery. This was documented by sonography, cholescintigraphy, and, ultimately, pathologically on the surgically removed specimen. Undoubtedly, with increasing cumulative treatment days made possible through technological advances in delivery systems, this complication will be seen more frequently. Prophylactic removal of the gallbladder, at the time of pump placement, which does not significantly prolong the operative time nor increase the operative mortality, should be performed to prevent this complication from occurring.

Adult↗
PubMed1986

Abnormal fetal behavioural state regulation in a case of high maternal alcohol intake during pregnancy.

In the near term human fetus disturbed behavioural state organization has been found in cases of intra-uterine growth retardation or maternal type-1-diabetes. The present case report describes abnormal fetal behavioural state organization found in combination with maternal alcohol abuse during pregnancy. The abnormalities included frequent interruptions of the periods of concordant association of 2F-parameters, reflected by a high proportion of no-coincidence, and spontaneous awakenings (State 4F), always following stable periods of State 1F. The latter phenomenon was not found thus far by us or others, neither in normal nor in complicated pregnancies. After birth normal state organization was found. It is suggested that the abnormalities in fetal behaviour might have been due to maternal alcohol abuse, whereas a possible withdrawal effect might have occurred in utero.

Adult↗
PubMed1986

Budd-Chiari syndrome complicating hepatocellular carcinoma. Demonstration by multiple radiotracer scintigraphy.

A case of hepatocellular carcinoma (HCC) complicated by the Budd-Chiari syndrome is described. The antemortem diagnosis of both conditions was made with the unique findings of multitracer scintigraphy. The difficulty of diagnosing these two conditions by the conventional approach is reviewed. The advantages of using multitracer scintigraphy for evaluation of hepatic lesions are also discussed.

Budd-Chiari Syndrome↗