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O Epstein

Publications and source records attributed to O Epstein.

At least 19 recordsLinked to original sources

A prospective study of colonoscopy practice in the UK today: are we adequately prepared for national colorectal cancer screening tomorrow?

AIM: To study the availability and quality of adult and paediatric colonoscopy in three National Health Service (NHS) regions. METHOD: A prospective four month study of colonoscopies in North East Thames, West Midlands, and East Anglia. PATIENTS: Subjects undergoing colonoscopy in 68 endoscopy units. RESULTS: A total of 9223 colonoscopies were studied. The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals. Intravenous sedation was administered in 94.6% of procedures, but 2.2% and 11.4% of "at risk" patients did not have continuous venous access or did not receive supplemental oxygen, respectively. Caecal intubation was recorded in 76.9% of procedures but the adjusted caecal intubation rate was only 56.9%. Reasons for failing to reach the caecum included patient discomfort (34.7%), looping (29.7%), and poor bowel preparation (19.6%). A normal colonoscopy was reported in 42.1%. The most common diagnosis was polyps (22.5%) followed by diverticular disease (14.9%). Inflammatory bowel disease was recorded in 13.9% and carcinoma in 3.8%. Only half of the patients remembered being told of possible adverse events prior to the procedure. Rectal bleeding requiring admission following colonoscopy was reported in six patients. The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure. Only 17.0% of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3% had attended a training course. CONCLUSION: There is serious under provision of colonoscopy service in most NHS hospitals. Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units. Colonoscopy is often incomplete and does not achieve the target 90% caecal intubation rate. Serious complications of colonoscopy were comparable with previous studies. Training in colonoscopy is often inadequate and improved practice should result from better training.

Adolescent↗

Gastric dysrhythmias occur in gastro-oesophageal reflux disease complicated by food regurgitation but not in uncomplicated reflux.

AIM: To investigate gastric pacemaker activity in gastro-oesophageal reflux disease using the electrogastrogram. PATIENTS: Forty patients with gastro-oesophageal reflux disease (20 with acid reflux, 20 with the additional symptom of food regurgitation) and 30 asymptomatic controls. METHODS: Patients were studied using an electrogastrogram, oesophageal manometry, and 24 hour ambulatory oesophageal pH analysis. RESULTS: An abnormal electrogastrogram was recorded in two (7%) controls, two (10%) patients with acid reflux, and 10 (50%) patients with food regurgitation. Food regurgitators had significantly more gastric dysrhythmias (tachygastrias) both before (p<0.02) and after (p<0.01) a test meal. Gastric pacemaker activity was also significantly less stable following the test meal in food regurgitators (p<0.003). Patients with food regurgitation and an abnormal electrogastrogram had higher oesophageal acid exposure than those with a normal electrogastrogram (p<0.05). CONCLUSIONS: The electrogastrogram is usually normal in gastro-oesophageal reflux disease but an abnormal rhythm occurred in half of our patients with the additional symptom of food regurgitation. Furthermore, an abnormal electrogastrogram is associated with increased oesophageal acid exposure.

Adult↗

Colonoscopy services in the United Kingdom.

BACKGROUND AND STUDY AIMS: Provision of a reasonable colonoscopy service requires approximately 160 procedures per 100000 population per year. The aim of the present study was to document current levels of colonoscopy service, the use of guidelines in surveillance practice and the capacity for expansion in endoscopy units throughout the United Kingdom. MATERIAL AND METHODS: A postal questionnaire was sent to 294 endoscopy units. RESULTS: Replies were received from 164 units (60 %). Of the units, 49 % have reached the calculated target figure. In units not meeting the target, 22% have only one colonoscopist, and 31% have one colonoscopy session a week. Overall, 50 % of units are working at full capacity. Out of all units, 70 % are unable to expand their service further, because of lack of nursing support in 81%, non-availability of endoscopist in 72 % and lack of physical space in 51%. Guidelines for surveillance colonoscopy were a problem: 51% of units reported that guidelines were available for surveillance of ulcerative colitis, 28 % for Crohn's disease, 59 % for polyp follow-up, and 44 % for follow-up of resected colorectal cancer. The majority of units (>70%) had no protocols for their surveillance practice. Nonetheless, 92% of units performed surveillance colonoscopy for ulcerative colitis, 34% for Crohn's disease, and 76% for resected colorectal cancer. CONCLUSIONS: The colonoscopy service has expanded, but there are constraints on further growth. There is a pressing need for national guidelines on surveillance colonoscopy.

Colitis, Ulcerative↗

Abnormalities of the electrogastrogram in functional gastrointestinal disorders.

OBJECTIVE: Cutaneous electrogastrography records gastric electrical activity and detects gastric arrhythmias. Abnormalities of the electrogastrogram have been described in a variety of disorders, but their specificity and their prevalence in patients with functional gastrointestinal disorders has not been reported. The aim of this study was to assess the specificity of electrogastrography as well as the prevalence and pattern of abnormalities in functional dyspepsia and irritable bowel syndrome. METHODS: Electrogastrography was performed in 170 patients with functional dyspepsia, 70 patients with irritable bowel syndrome, 20 patients with gastroesophageal reflux disease, and 30 asymptomatic controls. The abnormal electrogastrogram was defined as <70% normal electrical activity either before or after a test meal. RESULTS: The electrogastrogram was abnormal in 36% of patients with functional dyspepsia and in 25% with irritable bowel syndrome who complained of concurrent dyspepsia. The electrogastrogram was normal in 93% of asymptomatic controls, 90% of patients with gastroesophageal reflux, and 92% of patients with irritable bowel syndrome who did not complain of dyspepsia. As a group, functional dyspepsia patients had a greater degree of tachygastrias both before (p < 0.02) and after (p < 0.01) a test meal. The electrical frequency after the test meal was also more unstable (p < 0.003). CONCLUSIONS: The electrogastrogram is abnormal in approximately 36% of functional dyspepsia patients and has a specificity of approximately 93%. Electrogastrography defines a subgroup of patients with functional dyspepsia and electrical rhythm disturbance. In irritable bowel syndrome, the electrogastrogram is usually abnormal only if concurrent dyspepsia is present.

Adult↗

The effect of cisapride on dyspepsia symptoms and the electrogastrogram in patients with non-ulcer dyspepsia.

BACKGROUND: The electrogastrogram (EGG), which records gastric myoelectrical activity, is abnormal in one-third of adult patients with non-ulcer dyspepsia (NUD). AIM: To observe the effects of cisapride on EGG in adults with NUD. METHODS: Twenty-seven NUD patients who had undergone a pre- and post-prandial EGG were entered into an open study. All patients completed a dyspepsia symptom questionnaire and were then treated with cisapride 10 mg t.d.s. The dyspepsia questionnaire was repeated in all those completing 4 weeks of treatment. Those with an initial abnormal EGG (< 70% of slow wave activity at 2-4 cycles per minute) had a repeat EGG at the end of the study. RESULTS: Treatment with cisapride was associated with a significant improvement in the post-prandial EGG (P = 0.007). After 4 weeks of treatment, 7 of 13 abnormal EGGs normalized. Symptom scores improved significantly in the 13 patients with an abnormal EGG who completed treatment (P < 0.0003), but not in NUD patients with a normal EGG (P = 0.48). CONCLUSION: In this open study, treatment of NUD with cisapride was associated with significant symptom improvement in patients with an abnormal pre-treatment EGG, but not those with a normal EGG, with a significant improvement of the post-prandial EGG.

Adult↗

[Management of 29 children with thyroid cancer following the Chernobyl accident].

As a consequence of the Chernobyl nuclear power plant accident, a considerable increase of thyroid cancer among contaminated children has been reported in Ukraine, Belarus and Russia. A group of 29 children aged from 5 months to 10 years (mean 4.7 years) at the time of the accident, with a papillary thyroid cancer, have been examined at the Pitié-Salpêtrière hospital in Paris. The cancer was discovered by systematic ultrasonography in only 25% of cases. No reliable dosimetric estimation was achieved. The initial surgical treatment was performed in Ukraine. Cervical lymph node and pulmonary metastases were present in 24 and 11 cases respectively. A complementary surgical treatment was necessary for 9 children and one to four radioiodine treatments were given to 24 children. With a mean delay of 7 years after the cancer discovery, an apparent cure or a remission was obtained for 20 children, 6 children have cervical lymph node metastases requiring a surgical treatment and 3 have evolving lung metastases. The management of the great number of foreseeable cases of thyroid cancer requires an improved systematic screening, a large number of rooms dedicated to high activity radioiodine treatments, funds for disposable material and training missions.

Child↗

Levels of proteins C and S do not decline subsequent to first line chemotherapy in lymphoma patients.

Thromboembolic complications and decrease in protein C and S have been observed in patients while receiving combination chemotherapy for breast cancer. We investigated whether initial cytotoxic treatment of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is also associated with changes in these anticoagulant parameters. For this purpose 25 patients with intermediate to high grade NHL and seven with HD, undergoing primary treatment with cytotoxic drugs were evaluated at three time-points: pre-therapy, mid-therapy and post-therapy. In contrast to the breast cancer patients, no significant changes in protein C, protein S and antithrombin III levels were observed in the NHL patients during the various stages of therapy. However in HD patients, the mean protein C values had a tendency to be higher at mid-therapy compared to pre-therapy and protein S levels had a tendency to be higher at mid-therapy compared to post-therapy. In lymphoma patients receiving primary cytotoxic treatment we did not find changes in anticoagulant parameters that can explain a chemotherapy-induced hypercoagulable state, as has been reported in breast cancer patients.

Adolescent↗

Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine-induced haemolytic anaemia.

Haemolytic anaemia induced by phenylhydrazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference (Vm) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ-induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ-treated rats. PZ treatment did not influence mucosal reducing activity but Vm, measured using duodenal sheets, increased from -50 to -57 mV (P < 0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ-induced haemolytic anaemia.

Anemia, Hemolytic↗

Developmental changes in mucosal iron binding proteins in the guinea pig. Expression of transferrin, H and L ferritin and binding of iron to a low molecular weight protein.

Neonatal animals show an increased intestinal iron absorption despite being iron replete. We have used the developing guinea pig to determine whether alterations in the expression of iron binding proteins in duodenal enterocytes can account for the difference in iron absorption between neonatal and adult guinea pigs. No mRNA for transferrin was detected in the enterocytes. H ferritin mRNA remained constant from birth into adulthood whilst there was a small increase (< 2-fold) in L ferritin mRNA. Western blotting showed a clear increase in immunoreactive ferritin, levels reaching those of the adult 19 days after birth. We have also demonstrated that in the neonate, 80% of newly absorbed iron in the enterocyte is associated with a low molecular weight fraction (LMW-IBF), whereas in the adult, ferritin and LMW-IBF bind iron to the same extent. We conclude that changes in expression of ferritin during ontogeny are accompanied by a change in distribution of iron binding between ferritin and LMW-IBF implicating these proteins in the regulation of iron absorption.

Animals↗

Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study.

Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.

Biopsy↗

Evaluation of solvent/detergent treated plasma in the management of patients with hereditary and acquired coagulation disorders.

Haemostatic efficacy and pharmacokinetic analysis of solvent/detergent (S/D) treated, virus inactivated plasma (Octaplas, Germany) was evaluated in eight patients with hereditary factor VII, X and XI deficiency and in three patients with acquired coagulation disorders due to liver disease. The patients received the S/D plasma for treatment of haemarthrosis, menorrhagia or before surgical procedures. In all the patients the S/D plasma was sufficient to prevent or stop bleeding. Side effects included urticaria (one patient) and moderate anaphylactoid reaction (one patient). No evidence of plasma-born viral infections was observed up to 12 months after the treatment (95% confidence limits 0-22%). Calculated mean half-life of coagulation factors VII, X and XI was 4.36 h, 49.21 h and 44.5 h, respectively, similar to that observed with fresh-frozen plasma. Because of retained coagulation factor integrity and improved viral safety, S/D plasma could be considered a superior alternative to standard fresh-frozen plasma.

Adult↗

Induction of hepatic and pulmonary caeruloplasmin gene expression in developing guinea pigs following premature delivery.

We have previously shown that mRNA for caeruloplasmin, the serum copper-binding protein, is not expressed in guinea-pig liver prior to birth and expression increases rapidly following parturition. To further study the regulation of caeruloplasmin in neonatal animals we have used 3-day preterm guinea pigs, delivered by caesarean section, to investigate mRNA expression in liver and lung. Within 12 h of premature birth, hepatic caeruloplasmin mRNA levels are significantly increased and remain elevated by 72 h. This induction of expression is accompanied by an increase in circulating levels of holoprotein. Even greater induction of caeruloplasmin mRNA was observed in premature animals maintained in 95% oxygen for 72 h, confirming an acute-phase response in prematurity. Studies of lung RNA showed that caeruloplasmin mRNA is expressed throughout development, with highest levels observed in adult lung. In the premature animals levels were significantly elevated 12 h after delivery, but then fell by 72 h to below those seen in normal term lung. Hyperoxia did not influence the pulmonary mRNA levels.

Age Factors↗

Iron-transferrin binding to isolated guinea pig enterocytes and the regional localisation of intestinal iron transfer during ontogeny.

Neonatal animals are iron replete but in comparison with adults they display increased intestinal iron absorption. In order to examine possible mechanisms for this developmental adaptation we have measured the appearance of iron in peripheral blood following 30 min exposure of duodenal and ileal segments of adult and neonatal guinea pigs in vivo to 59Fe-ascorbate. Parallel experiments have determined the kinetics of 125I-labelled diferric transferrin binding to villus enterocytes isolated from duodenum and ileum. In adult animals the rate of appearance of 59Fe in peripheral blood was 11-fold greater following duodenal, compared to ileal exposure to the radioligand. No such regional difference was detected in the neonate. Isolated cells showed saturable binding of [125I]transferrin which was maximal between 30 and 60 min. The kinetics of specific transferrin binding by adult duodenal and ileal enterocytes were similar and were also not significantly different to respective values in neonatal duodenal and ileal cells. Thus, it is likely that increased iron absorption in the neonate is due in part to enhanced ileal iron transfer. The interaction of transferrin with its receptor, however, is not involved in this developmental change in uptake.

Animals↗

Copper metabolism in hypercupremic human livers. Studies of its subcellular distribution, association with binding proteins and expression of mRNAs.

In the present study we have used differential centrifugation, size exclusion chromatography, Western and Northern blotting to investigate the subcellular distribution of hepatic copper, the association of the metal with hepatic copper binding proteins and the expression of specific mRNAs for copper binding proteins in liver tissue from two patients with Wilson's disease, two patients with chronic liver disease and two patients with normal hepatic copper levels. Unlike previous studies the present results fail to show any gross differences in subcellular distribution of copper between the livers, with most of the copper being found in the soluble supernatant where it is associated with metallothionein. Caeruloplasmin mRNA levels were reduced in the two patients with Wilson's disease and also in a patient with fulminant hepatic failure. It remains to be confirmed if the reduction of caeruloplasmin mRNA is specific for Wilson's disease. Levels of mRNAs for copper zinc superoxide dismutase and metallothionein were variable and not related to liver copper.

Blotting, Northern↗

Regional characteristics of intestinal iron absorption in the guinea-pig.

Features of iron absorption by the upper small intestine and ileum in the adult guinea-pig have been compared. Autoradiographic methods have revealed that whilst only upper villus enterocytes in the duodenum-jejunum are involved in brush-border uptake, the entire villus epithelium in the ileum displays this function. Consistent with these results was the finding that brush-border membrane vesicles prepared from ileal mucosa demonstrated a higher capacity for iron uptake (expressed per mg protein) compared to vesicles of duodenal origin. Iron transport to blood following 30 min exposure of mucosa to 59Fe-ascorbate was some elevenfold higher in upper, compared to lower, small intestine. The relevance of these findings to our knowledge of the cellular processes involved in intestinal iron absorption and its regional localization is discussed.

Animals↗

Hepatic caeruloplasmin-gene expression during development in the guinea-pig. Correlation with changes in hepatic copper metabolism.

Decreased amounts of the serum copper-binding protein caeruloplasmin (hypocaeruloplasminaemia) are one of the characteristic abnormalities of copper metabolism that are found in all neonatal mammals. In the present study we have investigated the mechanism responsible for hypocaeruloplasminaemia found in neonatal guinea pigs. Northern-blot analysis of guinea-pig liver RNA revealed the presence of two caeruloplasmin mRNA species. A marked developmental change in expression was observed, with no detectable mRNA before birth, when hepatic copper is elevated. Expression was initiated soon after birth, when copper levels in the liver are falling, and was closely linked to the rise in enzymic activity and protein levels in serum. There was no differential regulation of the two mRNA species; however, a marked inter-animal variation in mRNA levels was observed. Using gel-filtration chromatography we were able to show that, before birth, serum copper was associated with a low-molecular-mass species and that, with the advent of expression of the caeruloplasmin gene after birth, copper was increasingly associated with caeruloplasmin.

Adult↗