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H Barr

Publications and source records attributed to H Barr.

At least 37 records · Page 2Linked to original sources
PubMed1999

Apoptotic and proliferative activity in the neoplastic progression of Barrett's oesophagus: a comparative study.

The balance between proliferation and apoptosis within a tissue is important in controlling its overall growth. When either or both are altered, uncontrolled cell proliferation can contribute to cancer. The aim of this study was to investigate apoptosis and proliferation in the progression from Barrett's oesophagus to adenocarcinoma. Fifty-one paraffin sections of Barrett's mucosa with both intestinal and gastric-type Barrett's mucosa, dysplasia, and adenocarcinoma, from 28 patients, were examined for apoptosis using haematoxylin and eosin (H&E)-stained sections counterstained immunohistochemically with CD45 to distinguish leucocytes from apoptotic bodies. Proliferation was detected by immunohistochemistry using the MIB-1 (Ki-67) antibody. There was an increase in proliferation in dysplastic and carcinomatous tissue compared with metaplastic tissue (p=0.0001). In dysplasia, proliferation was distributed throughout the basal-luminal axis, whereas in metaplasia, cell division was compartmentalized to the lower crypt (p<0.001). Conversely, there was a decrease in apoptosis in the upper crypt and luminal surface in dysplasia and adenocarcinoma compared with metaplasia (p<0.0008). There was a significant increase in apoptotic activity in intestinal-type Barrett's mucosa compared with gastric-type. There was a highly significant increase in the glandular proliferation to apoptosis ratio (GPAR) in the progression of metaplasia to dysplasia to adenocarcinoma (p=0.001). The shift in the GPAR in the progression of neoplastic change suggests that it may be a useful and sensitive marker of neoplastic change in Barrett's oesophagus, especially if the assessment of both apoptotic and proliferative activity in the mucosa can be made easier by more sophisticated technical methods.

Adenocarcinoma↗
PubMed1999

Laser ablation of ampullary carcinoma.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess whether the use of laser ablation could palliate or potentially cure ampullary carcinoma. PATIENTS AND METHODS: This study involved patients with confirmed ampullary carcinomas who were deemed fit for repeated endoscopic treatment but who were unfit for more radical treatment, and included six patients in Oxford and six in Gloucester. Repeated laser therapy was used after endoscopic stenting, following investigation as described. RESULTS: Good periods of survival were seen with good palliation and no complications of treatment. The longest survival was 36 months (range 4-36, median 21). Duodenal obstruction was successfully relieved in one patient. CONCLUSION: The treatment shows promise in selected patients, but conclusions are limited by the small numbers and lack of controls in this study.

Aged↗
PubMed1999

Multiple mechanisms of resistance to polyglutamatable and lipophilic antifolates in mammalian cells: role of increased folylpolyglutamylation, expanded folate pools, and intralysosomal drug sequestration.

Chinese hamster ovary PyrR100 cells display more than 1000-fold resistance to pyrimethamine (Pyr), a lipophilic antifolate inhibitor of dihydrofolate reductase. PyrR100 cells had wild-type DHFR activity, lost folate exporter activity, and had a 4-fold increased activity of a low pH folic acid transporter. Here we report on the marked alterations identified in PyrR100 cells compared with parental cells: 1) approximately 100-fold decreased folic acid growth requirement; 2) a 25-fold higher glucose growth requirement in Pyr-containing medium; 3) a 2.5- to 4.1-fold increase in folylpolyglutamate synthetase activity; 4) a 3-fold increase in the accumulation of [3H]folic acid and a 3-fold expansion of the intracellular folate pools; 5) a 4-fold increase in the activity of the lysosomal marker beta-hexoseaminidase, suggesting an increased lysosome number/PyrR100 cell; and 6) a small reduction in the steady-state accumulation of [3H]Pyr and no evidence of catabolism or modification of cellular [3H]Pyr. Consequently, PyrR100 cells were markedly resistant to the lipophilic antifolates trimetrexate (40-fold) and AG377 (30-fold) and to the polyglutamatable antifolates 5,10-Dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF) (26-fold) and AG2034 (14-fold). Resistance to these drugs was reversed in PyrR100 cells transferred into folate-depleted medium. In conclusion, these multiple resistance factors collectively result in a prominent increase in folate accumulation, an expansion of the intracellular folylpolyglutamate pool, and abolishment of the cytotoxic activity of polyglutamatable and lipophilic antifolates. The role of increased lysosome number per cell in sequestration of hydrophobic weak base drugs such as Pyr is also discussed as a novel mechanism of drug resistance.

Animals↗
PubMed1999

Beyond white light endoscopy--the prospect for endoscopic optical biopsy.

The most important factor in the successful treatment of cancer is early detection. This will be more likely to facilitate eradication of abnormal cells prior to systemic invasion. White light endoscopy has been an essential tool in medical diagnosis for a number of years. Direct endoscopic inspection of gastrointestinal organs has revolutionised diagnostic techniques, improving the targeting of biopsies of macroscopic morphological abnormalities. Recent technological developments are threatening a further revolution enabling the instantaneous and non-invasive diagnosis of microscopic tissue abnormalities in vivo. This is made possible by improving the level of information that can be obtained from the tissue. As well as the two-dimensional surface morphology image, which the traditional endoscope can view, new techniques enable structure at depth, i.e., the third-dimension, to be imaged in high resolution. Other advances enable the detection of biochemical changes in tissue that precede any changes in morphology, thus enabling earlier diagnosis of tissue abnormalities. This review details recent advances that have the greatest potential, for use in partnership with endoscopy, for the diagnosis of malignancy and pre-malignancy.

Biopsy↗
PubMed1998

The histopathology of treated Barrett's esophagus: squamous reepithelialization after acid suppression and laser and photodynamic therapy.

Columnar metaplasia of the lower esophageal epithelium (Barrett's esophagus) occurs in response to acid reflux, and its most important long-term complication is malignancy. In view of this, techniques are being explored for the eradication of Barrett's esophagus, and histopathologists will increasingly be required to assess response to these therapies in esophageal biopsy samples. The histopathologic features before and after treatment were studied in biopsy samples from 16 patients receiving omeprazole only, 10 treated by KTP laser photoablation, and five who underwent photodynamic therapy. All the treatment modalities resulted in histologic changes with at least partial squamous reepithelialization of the metaplastic columnar epithelium. The histologic findings suggest three main mechanisms for this: encroachment of adjacent squamous epithelium at the squamocolumnar junction, extension of epithelium from the submucosal gland duct to form squamous islands, and squamous metaplasia within the Barrett's columnar mucosa itself. The latter mechanism implies the existence of pluripotential stem cells within Barrett's mucosa. A relatively common finding was residual glandular mucosa, nonneoplastic and dysplastic, beneath squamous epithelium indicating the requirement for histologic confirmation of endoscopically suspected complete squamous reepithelialization with sufficiently deep biopsies.

Aged↗
PubMed1998

Altered cadherin and catenin complexes in the Barrett's esophagus-dysplasia-adenocarcinoma sequence: correlation with disease progression and dedifferentiation.

The maintenance of adult tissue architecture is largely dependent on the function of cadherins. E-cadherin is expressed in most epithelia, although it may be co-expressed with P-cadherin in basal layers of stratified epithelia. Adhesive function of cadherins relies on interactions with catenins. Many reports have characterized reduced expression of cadherins and catenins in tumors, including those of the gastrointestinal tract. This study aimed to characterize expression of E- and P-cadherins, and the catenins, in the progression of Barrett's esophagus to adenocarcinoma. Immunohistochemical analysis and Western blotting were performed on paraffin-embedded and fresh-frozen tissue using antisera to the selected cadherins and catenins. The results of this study have shown inappropriate expression of cadherins and catenins in neoplastic Barrett's mucosa. There was a significant reduction of E-cadherin expression as the Barrett's metaplasia-dysplasia-adenocarcinoma sequence progressed (P < 0.01). In contrast, P-cadherin, expressed in basal layers of squamous esophagus, was usually absent from Barrett's and dysplasia but was expressed in 17 of 24 carcinomas, especially at the advancing tumor edge. Reduced expression of catenins was also seen, but in some specimens, immunoreactivity was observed in neoplastic nuclei, suggesting mediation of a nuclear function such as transcriptional regulation.

Adenocarcinoma↗
PubMed1997

Palliation of malignant dysphagia by laser therapy.

The outcome of 211 patients undergoing laser therapy as palliation for inoperable carcinoma of the esophagus is presented. The median age was 73 (range 44-97). The histology was adenocarcinoma for 127 patients and squamous-cell carcinoma for 84 patients. For 133 patients, laser was the only therapy while 56 patients had a combination of laser therapy and radiotherapy/chemotherapy. One patient underwent laser recanalization prior to resection while four patients had recurrence after resection treated by laser. Eleven patients underwent laser therapy for recurrent dysphagia after placement of an esophageal endoprosthesis. Eighteen patients died of procedure-related complications (i.e. 9% of patients and 2% of procedures). Of 32 procedures which perforated the tumour, 10 ended in death and the remaining patients were successfully treated conservatively. Good palliation was achieved for 170 patients (80%), while 19 patients underwent intubation after failure of laser therapy. Laser therapy failed to relieve dysphagia for 22 patients. The median survival was 20 weeks with the 1-year survival 12% and 2-year survival 4%; there were no significant differences in survival dependent on histology or administration of adjuvant radiotherapy or chemotherapy. Laser therapy provides a practical alternative to intubation in the treatment of malignant dysphagia for patients with unresectable esophageal carcinoma.

Adenocarcinoma↗
PubMed1997

Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialisation.

BACKGROUND: Barrett's oesophagus is acquired by severe gastro-oesophageal reflux and is a premalignant condition. Acid suppression or anti-reflux surgery alone do not cause significant regression of the metaplastic mucosa nor reduce the malignant potential. Recent reports have suggested that the combination of mucosal ablation with acid suppression may result in squamous regeneration. AIMS: To destroy Barrett's mucosa by thermal ablation (in the setting of acid suppression) and so induce squamous regeneration. PATIENTS: Sixteen patients with non-dysplastic Barrett's oesophagus were recruited from a surveillance programme. All had been on a proton pump inhibitor. METHODS: At intervals, non-circumferential areas of columnar mucosa were ablated using the KTP laser. Acid suppression was obtained with 40 mg omeprazole daily. Multiple biopsy specimens were obtained for histological examination from ablated areas. RESULTS: Ablation of all areas of glandular mucosa resulted in squamous regeneration. The number of treatments required depended on the length of the Barrett's segment. In 11 patients there was evidence of squamous regeneration over remaining Barrett's glands (in some of the post-treatment biopsy specimens) whilst in nine patients squamous metaplasia was seen within Barrett's glands. CONCLUSION: Mucosal ablation of Barrett's oesophagus by laser, in the setting of acid suppression, results in squamous regeneration (though some burying of Barrett's glands did occur).

Adult↗
PubMed1996

Eradication of high-grade dysplasia in columnar-lined (Barrett's) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX.

BACKGROUND: High-grade dysplasia in columnar-lined (Barrett's) oesophagus presents a difficult therapeutic dilemma. Choices for management are endoscopic surveillance to detect a cancer or oesophagectomy. One carries the risk of missing invasive cancer, the other carries worrying morbidity and mortality. We have used endoscopic photodynamic therapy to eradicate high-grade dysplasia. METHODS: After the oral administration of 5-aminolaevulinic acid, the accumulation of the endogenously generated photosensitiser protoporphyrin IX was measured with quantitative fluorescence microscopy. Five patients with histologically confirmed high-grade dysplasia were treated with endoscopic photodynamic therapy with 630 nm laser light to activate the photosensitiser. FINDINGS: Protoporphyrin IX accumulated in the dysplastic epithelium rather than the adjacent stroma. Selective necrosis of the dysplastic epithelium in columnar-lined oesophagus occurred after light activation. High-grade dysplasia was eradicated in all patients and squamous regeneration occurred after acid suppression with a protonpump inhibitor. There were no complications or recurrence of dysplasia after 26-44 months' endoscopic and histological follow-up. In two cases we saw non-dysplastic Barrett's epithelium underneath regenerative squamous mucosa. INTERPRETATION: High-grade dysplasia in columnar-lined oesophagus can be eradicated by endoscopic photodynamic therapy with endogenously generated PpIX. Remaining non-dysplastic Barrett's epithelium will require surveillance, but overall the technique has interrupted or delayed the worsening of the dysplasia through to carcinoma. This technique may prevent the need for surgical excision in these patients.

Aged↗
PubMed1994

Cocaine exposure during pregnancy: improving assessment with radioimmunoassay of maternal hair.

OBJECTIVE: To compare radioimmunoassay of postpartum maternal hair samples with a structured maternal interview for the detection of cocaine use during pregnancy. METHODS: Radioimmunoassay of hair samples obtained postpartum was compared with self-report of cocaine use obtained by confidential, structured interviews of 405 postpartum women. RESULTS: Cocaine or benzoylecgonine was detected in the hair samples of 129 of the 148 women (87%) who reported using cocaine at least once during pregnancy. Thirty-six of 257 women (14%) who reported that they had used no cocaine during pregnancy had positive hair tests. Positive hair assay with negative self-report was significantly more common among women who were unmarried (P = .001), African-American (P < .001), and multiparous (P = .035). CONCLUSIONS: Hair analysis is a valuable complement to maternal self-report by interview. The methods used together provide a useful clinical and research technique yielding a comprehensive estimate of gestational cocaine exposure. Either method alone may result in misclassification of gestational cocaine exposure.

Adult↗
PubMed1992

Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization.

Photodynamic therapy (PDT) is often thought to be able to effect selective tumour necrosis. This therapeutic selectivity, based on transient differences in tumour: normal tissue photosensitizer concentration ratios, is rarely useful clinically in extracranial tumours, although PDT itself may be of value by virtue of the nature of the damage produced and healing of normal tissue by regeneration. This report describes the effects of PDT on normal pancreas and chemically induced pancreatic cancers in the hamster, where a different mechanism of selective necrosis may be seen. Photosensitizer distribution in normal and neoplastic pancreas was studied by chemical extraction and fluorescence microscopy. Correlation of distribution studies with necrosis produced by PDT shows that the photodynamic dose (product of tissue concentration of sensitizer and light dose) threshold for damage is seven times as high for normal pancreas as for pancreatic cancer. Tumour necrosis extended to the point where tumour was invading normal areas without damaging the normal tissue. In rat colonic cancer, photodynamic dose thresholds in tumour and normal tissue are similar and so such marked selectivity of necrosis is not possible. The reason for this selectivity in the pancreas is not clear, but recent evidence has suggested a difference in response to PDT between normal and neoplastic pancreatic cell lines and the presence of a singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the present fluorescence microscopy studies suggest that tumour stroma contains the highest level of photosensitizer and thus receives the highest photodynamic dose during PDT. These results suggest a possible role for PDT in treating small pancreatic tumours or as an adjuvant to other techniques, such as surgery, that reduce the main bulk of tumours localized to the pancreas.

Animals↗
PubMed1992

Management of synchronous arterial occlusions using intra-arterial thrombolysis.

Three patients presented with multiple acute arterial occlusions in separate limb vessels. The diagnosis was confirmed by angiography. Each patient was successfully treated by simultaneous infusion of low-dose intra-arterial streptokinase into each occlusion. All of the patients were improved clinically and in two patients completely normal pressure indices were restored.

Aged↗
PubMed1991

Prospective quality-of-life analysis after palliative photoablation for the treatment of malignant dysphagia.

Forty patients were treated for the relief of malignant dysphagia by using laser photoablation. Their quality of life was assessed before the start of treatment and at monthly intervals until death. Two methods were used, a physician's assessment (QL index) and a patient's self-assessment, the linear analogue self-assessment (LASA). There was significant correlation between assessments done at different times by different physicians (QL index rs, 0.786; P less than 0.001; LASA rs, 0.865; P less than 0.001). The correlation coefficient of the QL index and the LASA score with the patient's dysphagia grade was 0.459 and 0.336, respectively. The patient's swallowing ability, QL index, and LASA all were improved significantly at some time after laser therapy. The mean survival was 16 weeks with 58% of patients dying at home, 28% in the hospital, and 18% in a hospice. It was concluded that laser photoablation improves the overall quality of life in patients with malignant dysphagia.

Adult↗
PubMed1991

Intra-arterial thrombolytic therapy in the management of acute and chronic limb ischaemia.

A group of 54 patients with acute or chronic limb ischaemia were initially treated with low dose intra-arterial thrombolytic therapy using streptokinase (10,000 units h-1) or plasminogen activator (0.5 mg h-1). Complete thrombolysis was obtained in 90 per cent of patients with symptoms of less than 1 week duration, and in 50 per cent with symptoms of greater than 1 week (P less than 0.05). Successful lysis in 36 patients was followed by successful bypass surgery in seven, percutaneous angioplasty in 13, no further treatment in 13, repeat thrombolysis in two and amputation in one. Failed therapy was associated with major amputation in 40 per cent. One patient died of haemorrhage and another of stroke as a direct result of thrombolytic treatment. The most common complication was haematoma at the site of cannulation of the vessel. Intra-arterial thrombolytic therapy can be very useful for the management of acute and chronic limb ischaemia, but complications do occur and patients should be carefully selected.

Acute Disease↗