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Biomedical subjects

H Graffner

Publications and source records attributed to H Graffner.

At least 19 recordsLinked to original sources
PubMed2004

Natural history of gastro-oesophageal reflux disease diagnosed in general practice.

BACKGROUND: Cross-sectional studies indicate that gastro-oesophageal reflux disease symptoms have a prevalence of 10-20% in Western countries and are associated with obesity, smoking, oesophagitis, chest pain and respiratory disease. AIM: To determine the natural history of gastro-oesophageal reflux disease presenting in primary care in the UK. METHODS: Patients with a first diagnosis of gastro-oesophageal reflux disease during 1996 were identified in the UK General Practice Research Database and compared with age- and sex-matched controls. We investigated the incidence of gastro-oesophageal reflux disease, potential risk factors and comorbidities, and relative risk for subsequent oesophageal complications and mortality. RESULTS: The incidence of a gastro-oesophageal reflux disease diagnosis was 4.5 per 1000 person-years (95% confidence interval: 4.4-4.7). Prior use of non-steroidal anti-inflammatory drugs, smoking, excess body weight and gastrointestinal and cardiac conditions were associated with an increased risk of gastro-oesophageal reflux disease diagnosis. Subjects with gastro-oesophageal reflux disease had an increased risk of respiratory problems, chest pain and angina in the year after diagnosis, and had a relative risk of 11.5 (95% confidence interval: 5.9-22.3) of being diagnosed with an oesophageal complication. There was an increase in mortality in the gastro-oesophageal reflux disease cohort only in the year following the diagnosis. CONCLUSIONS: Gastro-oesophageal reflux disease is a disease associated with a range of potentially serious oesophageal complications and extra-oesophageal diseases.

Adolescent↗
PubMed2002

The role of the gut flora in health and disease, and its modification as therapy.

The gut flora is a vast interior ecosystem whose nature is only beginning to be unravelled, due to the emergence of sophisticated molecular tools. Techniques such as 16S ribosomal RNA analysis, polymerase chain reaction amplification and the use of DNA microarrays now facilitate rapid identification and characterization of species resistant to conventional culture and possibly unknown species. Life-long cross-talk between the host and the gut flora determines whether health is maintained or disease intervenes. An understanding of these bacteria-bacteria and bacteria-host immune and epithelial cell interactions is likely to lead to a greater insight into disease pathogenesis. Studies of single organism-epithelial interactions have revealed the large range of metabolic processes that gut bacteria may influence. In inflammatory bowel diseases, bacteria drive the inflammatory process, and genetic predisposition to disease identified to date, such as the recently described NOD2/CARD15 gene variants, may relate to altered bacterial recognition. Extra-intestinal disorders, such as atopy and arthritis, may also have an altered gut milieu as their basis. Clinical evidence is emerging that the modification of this internal environment, using either antibiotics or probiotic bacteria, is beneficial in preventing and treating disease. This natural and apparently safe approach holds great appeal.

Bacteria↗
PubMed2002

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

BACKGROUND: A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. METHODS: The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. RESULTS: Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). CONCLUSIONS: The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Absorptiometry, Photon↗
PubMed2000

Influence of smoking and Helicobacter pylori on gastric phospholipids.

Smokers show higher rates of peptic ulcer disease (PUD) than nonsmokers, probably due to detrimental effects on the gastric mucosa. Surface-active phospholipids (SPL) are believed to play a key part in gastric cytoprotection. The aim of this study was to determine the chronic effects of smoking on the gastric SPL and to relate them to H. pylori (Hp) -induced effects. Gastric juice was aspirated in 52 patients, with normal findings at planned upper gastrointestinal endoscopy, and concentrations of seven phospholipid subclasses were analyzed. Concentrations of lysophosphatidylethanolamine (1-PE) were increased (P = 0.006) in smokers compared to nonsmokers in non-Hp-infected samples. Nonsmokers infected with Hp showed increased levels of 1-PE (P = 0.01) and phosphatidylinositol (PI) (P = 0.02) compared to subjects not infected. In human gastric juice PI seems to be the dominating PL subclass, in contrast to the composition in biopsy specimens. We also found both Hp-infected and smoking subjects to have higher concentrations of more polar phospholipid subclasses, ie, 1-PE, making the mucosa more vulnerable to acid attack as the gastric surfactant becomes less hydrophobic.

Adult↗
PubMed2000

Treatment of joint pain in Crohn's patients with budesonide controlled ileal release.

1. Joint pain is a frequent manifestation of Crohn's disease. Budesonide controlled ileal release (CIR) is a predominantly topically acting glucocorticosteroid, which is effective in treating active ileal or ileocaecal Crohn's disease. 2. Therefore, it was of interest to study the effect of this predominantly topically acting therapy on the treatment of an extraintestinal symptom of Crohn's disease by analysing data collected from budesonide CIR (Entocort; Astra Draco AB, Lund, Sweden) trials. 3. Three large studies of budesonide CIR treatment in active Crohn's disease provided a reliable source of clinical data. Of the 611 patients treated in the prospective double-blind controlled trials, 291 had joint pain (arthritis/arthralgia) at entry, which was recorded as part of the Crohn's Disease Activity Index. Statistical analysis was based on all patients treated, provided that the patient had joint pain at the start of treatment. 4. Daily oral budesonide CIR (9mg) resulted in clinical remission of joint pain in 74% (95% confidence intervals (CI) 67-82%) of patients. This outcome was nearly twice as good as placebo (41%; 95% CI 34-57%) and as good as the outcome effected by daily oral prednisolone (40mg; 72%; 95% CI 60-84%). The favourable response to budesonide CIR (9 mg) did not correlate with glucocorticosteroid-associated side effects or with adrenal suppression, which were half those in the prednisolone (40 mg/day) group. 5. The favourable outcome may relate to restitution of normal intestinal immune function.

Administration, Oral↗
PubMed1999

Prospective randomized multicentre study of laparoscopic versus open appendicectomy.

BACKGROUND: A prospective randomized multicentre study was performed to compare the outcome of laparoscopic and open appendicectomy in patients with suspected acute appendicitis. METHODS: A total of 523 patients was randomized, but because of 23 withdrawals the outcome in 500 patients is reported, 244 in the laparoscopic group and 256 in the open group. RESULTS: Patients having laparoscopic appendicectomy recovered more quickly than those having open surgery (13 versus 21 days, P < 0.001). There was no significant difference in duration of sick leave after operation (laparoscopic group 11 days versus open group 14 days). Postoperative pain (at 24 h, 7 days and 14 days) was less after laparoscopic operations and a functional index 1 week after operation was more favourable in these patients (P < 0.001). Operating time was significantly longer in the laparoscopic group (60 versus 35 min, P < 0.01). Hospital stay and complications did not differ between the groups. Thirty laparoscopic procedures (12 per cent) were converted to open appendicectomy. CONCLUSION: Laparoscopic appendicectomy is as safe as open appendicectomy and has the advantage of allowing a quicker recovery.

Acute Disease↗
PubMed1997

Acute effects of high-dose intragastric nicotine on mucosal defense mechanisms: an analysis of nicotine, prostaglandin E2, phospholipase A2, and phospholipids.

Peptic ulcer disease is overrepresented among smokers; they also heal slowly and relapse frequently. Data are accumulating that smoking is detrimental to gastroduodenal mucosal cytoprotection. This study was designed to assess acute effects of high-dose intragastric nicotine, as it has been shown that nicotine is accumulated in gastric juice when smoking. Seven healthy smokers were given nicotine base (6 mg) as tablets, which yielded very high intragastric concentrations and plasma levels comparable to those seen when smoking. In addition to nicotine analysis, concentration levels of prostaglandin E2 (PGE2), phospholipase A2 (PLA2), and phospholipid classes were measured before and after nicotine administration. Nicotine inhibited PGE2 levels by 27-81%, whereas PLA2 and total phospholipids were unaffected. Lysolecithin, a degradation product of the main constituent of gastric surfactant, ie, phosphatidylcholine, tended to increase, but this was not reflected in intragastric phosphatidylcholine levels. In conclusion, nicotine acutely inhibits PGE2 and may thus impair mucosal cytoprotection. The present findings do not imply a central role of surface-active phospholipids with respect to nicotine and gastric cytoprotection, but the chronic effects of nicotine remain to be investigated.

Adult↗
PubMed1996

The anti-ulcer drug sucralfate does not affect gastric nicotine levels.

OBJECTIVE: It has been claimed that sucralfate can overcome the negative effects of nicotine in patients with peptic ulcer disease, although the possible mechanism being unknown. This study was performed in order to test whether sucralfate was capable of binding intragastric nicotine, thus making it impossible for the substance to exert effect. METHOD: Nicotine was administered via transdermal patches or as capsules yielding gastric concentrations of 40-2980 ng.ml-1. Gastric juice aspirates (n = 9) were incubated with sucralfate, which was then separated by centrifugation, and the nicotine concentration was compared in incubated and non-incubated samples. RESULTS: A median decrease of 13% (range 0-27%) in nicotine concentration was seen after incubation with sucralfate (P = 0.01). CONCLUSION: The binding of nicotine to the precipitating agent sucralfate is not sufficient effectively to remove nicotine from the gastric juice.

Administration, Cutaneous↗
PubMed1996

Transdermally administered nicotine accumulates in gastric juice.

METHODS: Transdermal nicotine patches (Nicorette 15 mg.16 h-1) were administered to 7 healthy volunteers. Nicotine concentrations in gastric juice were monitored for 8 h via a naso-gastric tube and so was nicotine in saliva and plasma. RESULTS: Nicotine accumulated in gastric juice, the average concentration being 60.6-times higher than in plasma. In saliva, too, the concentration was higher than in plasma, the average ratio being 10.5. These results strongly suggested ion-trapping of nicotine base in the acidic gastric juice and possibly also in the acinar cells, followed by active secretion. It is hypothesised that accumulation in saliva occurs via a similar mechanism. Pretreatment with omeprazole did not increase the pH to a sufficiently high degree to test the hypothesis that the accumulation of nicotine in gastric juice was pH dependent. CONCLUSION: Transdermal administration of nicotine produced a high intragastric concentration. The clinical consequence of this effect of long-term nicotine replacement therapy during smoking cessation is unclear.

Administration, Cutaneous↗
PubMed1995

A financial analysis of laparoscopic and open cholecystectomy.

Laparoscopic cholecystectomy (LC) is now the method of choice in treatment of symptomatic gallstone disease. Despite its rapidly growing popularity, comparative costs of this new method and open cholecystectomy (OC) remain unclear. The most outstanding feature of laparoscopic cholecystectomy is the period of short recovery. In Sweden the social insurance office documents sick leave period, sickness allowance, as well as diagnosis and therefore provides a reliable basis for an economic analysis. The purpose of this study was to estimate the hospital cost and costs due to sick leave in a series of patients operated on with elective cholecystectomy using the two methods. In each group 50 consecutive patients were studied retrospectively. The total hospital cost was 10% lower in the laparoscopy group--$1,864 as compared to $2,030 per patient in the OC group. Median number of days off work was 14 after LC and 35 days after open surgery, which corresponds to a median sickness allowance of $516 per patient (LC) compared to $1,424 (OC). Laparoscopic cholecystectomy is more cost-effective than open cholecystectomy mainly due to a reduced sick leave period.

Adolescent↗
PubMed1995

Follow-up after curative surgery for colorectal carcinoma. Randomized comparison with no follow-up.

PURPOSE: This study investigated the value of intense follow-up compared with no follow-up after curative surgery of cancer in the colon or rectum. METHODS: One hundred seven patients were randomized to no follow-up (control group; n = 54) or intense follow-up (follow-up group; n = 53) after surgery and early postoperative colonoscopy. Patients in the follow-up group were followed at frequent intervals with clinical examination, rigid proctosigmoidoscopy, colonoscopy, computed tomography of the pelvis (in patients operated with abdominoperineal resection), pulmonary x-ray, liver function tests, and determinations of carcinoembryonic antigen and fecal hemoglobin. Follow-up ranged from 5.5 to 8.8 years after primary surgery. RESULTS: Tumor recurred in 18 patients (33 percent) in the control group and in 17 patients (32 percent) in the follow-up group. Reresection with curative intent was performed in three patients in the control group and in five patients (four of whom were asymptomatic) in the follow-up group. In the follow-up group two asymptomatic patients with elevated carcinoembryonic antigen levels were disease-free three and five and one-half years after reresection and were the only patients apparently cured by reresection. No patient underwent surgery for metastatic disease in the liver or lungs. Symptomatic metachronous carcinoma was detected in one patient (control group) after three years. Five-year survival rate was 67 percent in the control group and 75 percent in the follow-up group (P > 0.05); the corresponding cancer-specific survival rates were 71 percent and 78 percent, respectively. CONCLUSION: Intense follow-up after resection of colorectal cancer did not prolong survival in this study.

Aged↗
PubMed1994

Budesonide versus prednisolone retention enemas in active distal ulcerative colitis.

METHODS: Efficacy and safety of the topically acting glucocorticosteroid budesonide retention enema (2.3 mg/115 mL) were compared with prednisolone disodium phosphate enema (31.25 mg/125 mL) in patients with active distal ulcerative colitis. The study was a randomized, multicentre trial, with two parallel groups and single-blind to the investigator. One hundred patients with active ulcerative colitis, not reaching beyond the splenic flexure as determined by endoscopy, were treated for up to 8 weeks. RESULTS: Forty-five patients were randomized to receive budesonide and 55 to prednisolone. Both treatment groups improved significantly in terms of endoscopic and histological scoring during the study, but there were no statistically significant differences between the two groups. Clinical remission, defined as no more than three daily bowel movements without blood and endoscopically non-inflamed mucosa, was achieved in 16% of the patients in the budesonide group after four weeks and in 24% in the prednisolone group (N.S.). After 8 weeks treatment the clinical remission rate in the groups had increased to 36% for budesonide and 47% for prednisolone (N.S.). Mean morning plasma cortisol levels were unchanged in the budesonide group, whereas they were significantly suppressed in the prednisolone group after 2, 4 and 8 weeks (P < 0.0001). Side effects were mild and rare in both groups. CONCLUSIONS: Treatment with budesonide enema in active distal ulcerative colitis was comparable, regarding efficacy, to treatment with conventional prednisolone enema. A prolongation of the treatment time from 4 to 8 weeks doubled the clinical remission rate in both groups. However, budesonide may be preferable to prednisolone since it causes less systemic effects as reflected by a lack of plasma cortisol suppression.

Adult↗
PubMed1994

On the natural history of peptic ulcer.

BACKGROUND: Three out of 1000 individuals have peptic ulcer every year, and 20% of the ulcer episodes are associated with bleeding. Whether major innovations such as endoscopy and strong acid-suppressing drugs have had any impact on the natural course of peptic ulcer disease is largely unknown. METHODS: Three hundred and fifty-one patients (median age, 63 years) with endoscopically proven peptic ulcer during 1979-1984 were included in the study and retrospectively followed up via medical records. The total population is based on two different groups of patients, the first comprising 229 consecutively diagnosed ulcer patients during 1979-81 and, to increase the number of bleeders, a second group including 122 bleeding ulcer patients consecutively diagnosed during 1981-84. At the end of the follow-up period all non-ulcer-operated patients were asked to answer a questionnaire on symptoms, investigations, and medication. RESULTS: The male to female ratio was 2.4:1 in duodenal ulcer patients, but a 1:1 ratio was shown both in gastric and prepyloric/pyloric ulcer patients (p < 0.001). Patients with bleeding ulcers were significantly older than non-bleeders (68 years versus 58 years; p < 0001), as were patients with gastric ulcers compared with prepyloric/pyloric or duodenal ulcer patients (68 years versus 63 and 61 years, respectively; p < 0.01). The 10-year cumulative mortality in the unselected group (median age, 62 years) was 43%, and the annual risk of dying of peptic ulcer disease was 0.6%. No difference in 10-year recurrence rate was seen between patients with bleeding ulcer at inclusion and non-bleeders (46.2% versus 44.3%; p = NS), but the annual risk of bleeding was 5.3% and 0.8%, respectively (p < 0.0001). In the group of patients answering the questionnaire 51% reported upper abdominal pain during the last year of follow-up. CONCLUSIONS: In spite of today's treatment regimens almost half of the patients with peptic ulcer disease experienced recurrence during a 10-year period, and more than half had ulcer symptoms after 10 years. Most probably, maintenance treatment with H2-receptor antagonists should have been offered more liberally during the 1980s.

Age Factors↗
PubMed1993

Acute effects of smoking during modified sham feeding in duodenal ulcer patients. An analysis of nicotine, acid secretion, gastrin, catecholamines, epidermal growth factor, prostaglandin E2, and bile acids.

Smoking is associated with an increased incidence of duodenal ulcer with a high relapse rate, and smokers tend to be slow healers. The etiology responsible for this remains unknown, and there is general disagreement as to whether smoking affects gastric secretion. The aim of the present study was to investigate both aggressive and protective factors in response to vagal stimulation induced by modified sham feeding (MSF) in duodenal ulcer patients when smoking versus not smoking. On smoking days, nicotine concentrations in plasma averaged about 15 ng/ml and were extremely high in saliva and gastric juice (> 1300 and > 800 ng/ml, respectively). MSF induced a significant decrease in intragastric pH during non-smoking (p = 0.01) but not during smoking. Acid output 1 h after MSF was lower on smoking than on non-smoking days (p = 0.02), as was volume secretion (p = 0.02). Plasma gastrin concentrations were significantly increased during MSF on non-smoking days (p = 0.04) but not on smoking days, the concentrations during the whole day being lower on smoking days (p = 0.002). Plasma catecholamine levels were unaffected by MSF, whether smoking or not. However, plasma concentrations of noradrenaline decreased during the smoking of a single cigarette (p = 0.03), whereas those of adrenaline were increased on smoking days (p = 0.02). Epidermal growth factor concentrations were decreased in gastric juice after MSF during non-smoking (p = 0.01) but not during smoking. Although prostaglandin E2 (PGE2) concentrations in gastric juice were unaffected by MSF, PGE2 output increased after MSF whether smoking or not, the increment being non-significantly less during smoking (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗
PubMed1992

Omeprazole-induced hypergastrinemia does not influence growth of colon carcinoma.

Colonic mucosa and adenocarcinoma are known to possess gastrin receptors. Recent studies have suggested that some patients with large intestinal cancers and polyps have elevated serum gastrin levels and that gastrin may stimulate growth of colonic neoplasms. The aim of the present investigation was to determine whether endogenous hypergastrinemia--induced by the proton pump inhibitor omeprazole--would influence growth in a subcutaneously implanted murine colonic cancer. The results show that despite a fivefold increase in serum gastrin levels (193 pg/ml median value, range 186-252, in the omeprazole-treated group vs 36 pg/ml median value, range 28-37 in controls), there were no differences in tumor size or survival of tumor-bearing animals. Additionally, there were no differences in serum gastrin values between tumor- (29 pg/ml, range 25-38) and non-tumor- (34 pg/ml, range 25-30) bearing, untreated animals. Endogenous elevation of the serum gastrin hormone to five times the normal level does not demonstrate trophic effects on the murine colon tumor MC-26.

Adenocarcinoma↗