Antibiotic prescribing practices among Norwegian dentists.

There is scarce information on antibiotics prescription habits among dentists in general. The present investigation was undertaken to study some patterns of antibiotics prescription among Norwegian dentists. A total of 459 dentists (approximately 10% of Norwegian dentists) were randomly selected, and to each was mailed a letter describing the survey, accompanied by a questionnaire about age, type of practice, educational background and pattern of prescription of antibiotics. 78% of the dentists responded to these questions. The results indicate that during a typical week, 32% did not prescribe antibiotics, whereas 5% wrote greater than 5 prescriptions. The mean weekly number of prescriptions per dentist was 2.04. Periodontists and oral surgeons prescribed antibiotics significantly more often than did general practitioners and other disciplines. In addition, those with research and/or teaching experience seemed to prescribe significantly more often than those without. More than 1/3 of the sample indicated that they may prescribe antibiotics when treating periodontal diseases. Compared with other disciplines, periodontists prescribed such drugs significantly more often when treating periodontitis, but significantly less often in acute gingivitis, stomatitis and herpes simplex infections. Moreover, 22% of the dentists might prescribe antibiotics when the patient is in pain, 73 and 38% in cases of abscesses with or without generalized malaise, 2.5% in endodontic therapy, 60% to prevent general complications, and 68% for prophylactic use if the patient revealed a history of endocarditis. Norwegian dentists are somewhat restrictive in their prescription of antibiotics, but they mostly prescribe the correct drugs for the different conditions.


Epithelial adherence to polytetrafluoroethylene (PTFE) material.

The aim of this study was to examine adherence/attachment of gingival cellular elements to polytetrafluoroethylene (PTFE) material with special reference to epithelial cells. Six Gore-Tex membranes used for guided tissue regeneration in patients with severe periodontal disease were studied by transmission electron microscopy. Upon retrieval, after 30 days of healing, the membranes were immediately immersed in formaldehyde-glutaraldehyde, divided in segments (2 x 4 mm) and embedded in Epon. The majority of segments were devoid of any adhering tissue other than erythrocytes and polymorphonuclear cells. Epithelial cell adherence was mediated by a 2-microns-thick acellular layer containing membraneous profiles with diameter 370 nm or less. Adhering epithelial cells exhibited characteristics of cellular degeneration as evidenced by tonofilamentous and cytoplasmic condensation, vacuolization and loss of structural details. An uneven basement lamina with hemidesmosomal contacts was present at the epithelium-connective tissue interface. It is concluded that epithelial cells adhere to PTFE material without formation of attachment complexes.


Integrated currents between amalgams and a gold alloy in saline solutions and natural saliva with different chloride content.

The effect of different sodium chloride concentrations on the integrated currents (charge transfers) between dental amalgams and a gold alloy was studied in a bimetallic cell containing saliva or saline solutions. The integrated currents were only to a minor degree affected by increasing chloride concentrations for the high copper amalgams both in saliva and saline solutions. The integrated currents in the experiments involving conventional amalgam were several times higher than those for high copper amalgams. In saline solutions a charge transfer maximum was found at 0.2 M chloride. In saliva an increase of the charge transfer was found with increasing chloride content.


Five-year study of cervical erosions restored with resin and dentin-bonding agent.

The cumulative retention rate of a microfilled resin in non-undercut cervical abrasion/erosion lesions was studied over a 5-yr period. The enamel was etched and the dentin was pretreated with either Gluma (n = 75) or the first marketed version of Scotchbond (n = 30). The cumulative 5-yr retention rate of the Gluma fillings was 90% and that of the Scotchbond fillings 47% (the 95% confidence limits were 83-98% for Gluma fillings and 27-67% for Scotchbond fillings). The retention rate with both bonding agents was significantly higher in the maxillary arch than in the mandibular arch.


Fructose and related food carbohydrates. Sources, intake, absorption, and clinical implications.

It is possible to point out subjects consuming considerable quantities of fructose and sorbitol, and the intake seems to be increasing both from added and natural sources. Studies of the absorption of fructose in animals are inconsistent, and the mechanisms of fructose uptake seem to vary in accordance with the species. In most species fructose absorption takes place by a specific carrier (facilitated transport), but it may be active in the rat. In vitro studies of human intestine are very scarce; there is no evidence of active intestinal fructose transport in the human intestine. By means of hydrogen breath tests, a very low absorption capacity for fructose given as the free monosaccharide has been found in humans. Fructose given as sucrose or in equimolar combinations with glucose is well absorbed, and only fructose in excess of glucose is malabsorbed. On this basis it is hypothesized that two different uptake mechanisms for fructose are present in the human intestine. One of these may be a disaccharidase-related uptake system. Sorbitol ingestion may aggravate malabsorption of fructose given as the monosaccharide; it is not known whether a specific mechanism is involved. In children and adults with functional bowel distress the absorption capacities for fructose may not differ from those of healthy individuals, but malabsorption of fructose and/or sorbitol may be the cause of or aggravate abdominal symptoms. Fructose polymers (fructans) are also subject to increasing nutritional interest. Fructans are not absorbed in the small intestine but are strongly fermented in the large bowel. Fructans may be of potential benefit for large-bowel function and blood glucose regulation.


The effect of portal perfusion on intrasplenic hepatocytes.

A newly developed rat model of portal diversion, in which the subcutaneously transposed spleen is perfused by splanchnic effluent as a result of portal vein ligation, has been used to monitor the effect of such portal perfusion on intrasplenic hepatocyte implants. Three groups of animals (controls, n = 42; transposed only, n = 70; and portally diverted, n = 58) received 2 million syngeneic liver cells. The number of hepatocytes in each spleen was assessed 5 days to 9 months later by direct counting of splenic sections. The transposed spleen was capable of supporting hepatocyte grafts even over long periods, although the number of cells was reduced in comparison with controls. Diversion of portal flow across the transposed spleen significantly increased hepatocyte numbers in the first 6 weeks (median number of cells (with inner quartile range), 1380 (70-1300) versus 600 (347-4050); n = 75), but no differences were detected thereafter. It appears that the initial lag phase of hepatocyte grafts can be partially abrogated by portal perfusion, but the subsequent 'proliferative' phase is unaffected. These effects correlate well with established theories on the importance of portal flow to the intact liver.


The anatomic range of examination by fibreoptic rectosigmoidoscopy (60 centimetres).

The purpose of the study was to investigate the anatomic location of the flexible rectosigmoidoscope (60 cm) when introduced as far as technically possible. One hundred and forty-nine consecutive patients referred for double-contrast enema (DCE) were examined with rectosigmoidoscopy before the radiologic examination, and CO2 was used for insufflation. A plain abdominal film was taken to locate the tip of the instrument when 60 cm or as much as possible of the instrument had been introduced. The sigmoid loop was passed and the tip of the scope located in the ascending colon or at the left flexure in 99 (66%) of the patients, and in a further 27 (18%) the upper part of the sigmoid colon was reached. The sigmoid colon had been passed in 71%, 80%, and 44% when 60, 50, and 40 cm of the instrument was introduced, respectively. DCE could be performed at the same session as the rectosigmoidoscopy, as CO2 was quickly absorbed. In the vast majority of patients the sigmoid colon can be inspected with a rectosigmoidoscope.


Proliferative activity of bile duct epithelium after bacterial infection in dogs.

To clarify the relationship between proliferative activity in bile duct epithelia and bacterial infection in the dog, we induced obstructive cholestasis with a bacterial infection in two lobes of the liver. The bile duct branch draining the left lateral lobes of the liver was cannulated in all mongrel dogs. The dogs were divided into three groups and treated as follows: in group 1 the cannula was clamped after the injection of 10(7) Escherichia coli (aerobic bacteria) and 10(7) Bacteroides fragilis (anaerobic bacteria) cells; in group 2 the cannula was clamped after the injection of 10(7) E. coli cells; and in group 3 the cannula was clamped without the injection of any bacteria. Three months and 9 months later dogs from each group were killed, and their livers were examined. In the group 1 dogs papillary hyperplasia and severe dysplasia were noted in association with chronic cholangitis at 3 months and 9 months, respectively, after operation. In the group 2 dogs periductal fibrosis was severe, but epithelial papillary hyperplasia was less pronounced than in the group 1 dogs at each period. In the group 3 dogs no periductal fibrosis or epithelial papillary hyperplasia was seen at either 3 or 9 months postoperatively. These findings suggest that papillary hyperplasia and/or severe dysplasia of the bile duct epithelium may be caused by aerobic and anaerobic bacterial infection of the biliary tract in combination with bile stasis.


1-year survey of patients with advanced liver cirrhosis. Prognostic value of clinical and laboratory indexes identified by the Cox regression model.

The relation between coagulation indexes and survival rate was studied and analyzed in 46 patients with advanced liver cirrhosis (grade B and C Child-Pugh Classification), during a follow-up of 1 year. Twenty-four patients (52%) died of liver failure or fatal haemorrhage within 12 months of follow-up. Prothrombin activity, fibrinogen, fibrin(ogen) degradation products, prekallikrein and factor VII, serum bilirubin, and the degree of liver insufficiency, scored by Child-Pugh classification, proved to be significantly correlated with survival by univariate analysis. A multivariate survival analysis (Cox regression model) disclosed two variables, prekallikrein and factor VII, that predicted survival. The rate ratios of death increased to 2.8 and 7.6 with values of prekallikrein < 26% and factor VII < 39%, respectively. This study shows that some simple laboratory tests exploring the clotting system may identify patients with poor prognosis in severe liver failure.


Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects.

We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (micrograms/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D50) was similar before (0.060 micrograms/kg/h) and after (0.057 micrograms/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/l (range, 22-77) before treatment and fell to 33 ng/l (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function.


Suppression of anger and gastric emptying in patients with functional dyspepsia.

Psychologic distress and gastric motor dysfunction have both been implicated in the pathogenesis of functional (non-ulcer) dyspepsia (FD). This study assesses the association between psychologic factors and gastric emptying in 28 FD patients. Subjects completed an extensive range of psychologic questionnaires and underwent dual-isotope scintigraphic assessment of solid and liquid gastric emptying. Attempts to resist, control, suppress, and hold in anger, to adopt a fighting spirit whilst dealing with chronic stressors, and manifest unhappiness were predictors of prolonged gastric emptying. These findings suggest that psychologic factors may be important in the aetiology of gastric stasis and subsequent upper gastrointestinal symptoms in patients with functional dyspepsia.


Stereologic investigations of human gastric mucosa. II. Oxyntic mucosa from patients with Zollinger-Ellison syndrome.

Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia, dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were lingulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects.


Location and type of gastric carcinoma in relation to pepsinogen I level in blood.

Serum pepsinogen I (PGI) levels were measured in 192 gastric carcinoma (GC) patients and 70 controls. Among GC patients serum PGI levels were not influenced by the following variables: age, sex, smoking, Borrmann's or Lauren's classification, tumor size, cellular differentiation, and layer of invasion. The mean serum PGI levels of tumors restricted to the body, antrum, or involving both areas were 64.8 +/- 37.6 ng/ml, 76.0 +/- 47.0 ng/ml, and 51.1 +/- 25.5 ng/ml, respectively (P < 0.005). Odds ratios of GC patients from the quartile of 262 serum PGI levels in the limits > or = 100 ng/ml, 70-99.9 ng/ml, 45-69.9 ng/ml, and < 45 ng/ml were 1.00, 0.76, 3.44, and 37.1, respectively (P < 0.001). The lower serum PGI levels of Chinese GC patients seem to be related to disease location rather than other characters of the tumor.


Computer-aided decision support in hepatology.

The aim of this study was to describe and to evaluate the publications of the last 30 years devoted to computer-aided decision support in clinical hepatology. The search used Medlars and references of articles. Computer-aided decision support (CADS) was classified in two categories: statistical systems and knowledge-based systems. Two specific questionnaires were used for methodologic evaluation, one for statistical systems and one for knowledge-based systems. They were filled out independently by two observers. A total of 31 papers were selected among 55 identified between 1960 and 1991. The maximum possible for the two scores was 24. The methodologic quality ranged from 4 to 22 (median, 12) for statistical systems and from 8 to 12 (median, 9) for knowledge-based systems. The poor level of methodology could explain in part the lack of utilization of computer-aided decision support in the daily clinical practice of hepatologists.


Absorption of wheat starch in patients resected for left-sided colonic cancer.

Bacterial fermentation of carbohydrate in the colon, producing short-chain fatty acids (SCFA)--and especially butyrate--has been shown possibly to impede cell proliferation and regulate cell differentiation of colonocytes. In patients with diverticular disease or benign polyps in the colon a hyperabsorption of potato starch in the small intestine has been found. We have investigated the absorption of wheat starch in 15 patients radically resected for cancer in the descending or sigmoid colon, and the results were compared with those of 15 healthy controls. The starch malabsorption was quantified by the hydrogen breath test. The patients malabsorbed 2-14 g (median, 8 g) of 100 g wheat starch ingested, and the control group malabsorbed 3-11 g (median, 6 g) (P greater than 0.1). Mouth-to-cecum transit time for wheat starch and lactulose and the hydrogen production capacity after the lactulose standards were also similar in patients and controls. The results do not support the theory that hyperabsorption of starch is characteristic of patients with malignant disease in the large intestine.


Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury.

Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5-100 micrograms/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID50 for ethanol- and stress-induced lesions after TGF were 40 and 70 micrograms/kg-h and after EGF 60 and 100 micrograms/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E2 (PGE2). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE2 by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS)


Argyrophil cells, mast cells, and histamine in the fundic mucosa of antrectomized patients.

Fasting gastrinemia, fundic argyrophil cell density, mast cell number, basal fundic histamine content and histidine decarboxylase activity were determined in 20 antrectomized patients and 20 control subjects. Fasting gastrinemia and fundic argyrophil cell density were significantly lower in antrectomized patients than in controls, whereas fundic mast cell number, basal histamine content, and histidine decarboxylase activity did not differ significantly between the two groups. In antrectomized patients the basal fundic histamine content appears related to the fundic mast cell number, as a consequence of the reduced effect of gastrin on argyrophil cells.


Colonoscopic screening examination of relatives of patients with colorectal cancer. I. A comparison with an endoscopically screened normal population.

First-degree relatives (n = 206) of patients operated on for colorectal cancer (CRC) (n = 181) were offered a colonoscopic screening examination; 169 relatives (82%) attended. The findings were compared with those in a normal population sample with no CRC in first-degree relatives (n = 308), aged 50-59 years, who had been screened by means of flexible sigmoidoscopy. Three carcinomas and 176 polyps were found in 56 of 95 male relatives (57%) and 34 of 74 female relatives (46%). The adenoma prevalence rate was 37 (39%) and 26 (35%) for male and female relatives, respectively. In the 50- to 59-year age group, the adenoma prevalence rates for both sexes collectively and for women separately were significantly higher among relatives than among the population without CRC relatives. Hyperplastic polyps were larger, whereas adenomas were similar in size among relatives compared with the normal population. Colonoscopy may be a suitable method of choice for screening first-degree relatives of patients with CRC.


Colonoscopic screening examination of relatives of patients with colorectal cancer. II. Relations between tumour characteristics and the presence of polyps.

Colonoscopy was offered to 206 first-degree relatives of 181 patients operated on for colorectal cancer (CRC). Findings of polyps in relatives correlated with Dukes staging, extent of dedifferentiation and localization of tumour in the operated patient, and type of family relationship. Adenomas in relatives and Dukes staging of carcinoma in the patients were inversely related. Relatives of patients with Dukes stage A tumour had more than twice as many adenomas as and a higher prevalence of multiple adenomas than relatives of patients with advanced cancer at the time of operation. If the patient had polyp(s) in addition to tumour, the number of adenomas per relative was almost doubled. Hyperplastic polyps in relatives were associated with poorly differentiated carcinoma in their related patients. These results support the theory that not all CRC are derived from polyps and that adenoma-derived CRC may have a better prognosis than 'de novo' CRC. An adenoma prevalence risk table is also presented.


Effect of platelet-derived growth factor-BB on indomethacin-induced gastric lesions in rats.

The effect of platelet-derived growth factor-BB (PDGF-BB) was evaluated in rats with indomethacin-induced gastric lesions. Animals were treated with either saline solution or several doses of PDGF-BB given orally. Rats treated with 0.1 nmol/kg PDGF-BB showed a statistically significant reduction of gastric damage. Higher doses did not produce any further reduction of gastric damage, and a return toward control values was observed. The effect on lesions was independent of inhibition of gastric acid secretion, since a dose of 0.1 nmol/kg of this growth factor failed to modify gastric acid secretion stimulated by pylorus ligation.


Increased protein tyrosine kinase activity of the colonic mucosa in ulcerative colitis.

The protein tyrosine kinase (PTK) activity was measured in the inflamed colonic mucosa of 12 patients with ulcerative colitis and in the normal colonic mucosa of 12 control patients with colon cancer. The specific PTK activity in the particulate fraction obtained from ulcerative colitis mucosa was significantly increased compared with that of normal mucosa (5.10 +/- 0.60 pmol/min/mg versus 2.12 +/- 0.44 pmol/min/mg protein; p less than 0.05). Inflamed ulcerative colitis mucosa also showed a significantly higher total PTK activity in the particulate fraction than normal mucosa (2.60 +/- 0.42 pmol/min/g versus 0.91 +/- 0.16 pmol/min/g tissue; p less than 0.05). Mucosal samples from ulcerative colitis patients were divided into those with mild and those with severe inflammation on histologic examination (n = 6 each). The particulate PTK activity of severely inflamed mucosa was significantly higher than that of mildly inflamed mucosa (p less than 0.05). These results suggest that colonic inflammation in ulcerative colitis is associated with alterations in cellular PTK activity.


Initiation of anastomotic recurrence of Crohn's disease after ileocolic resection. Onset proximal to the junction and preceded by increased phospholipase A2 activity.

Colono-ileoscopy was performed on 11 patients after ileocolic resection for Crohn's disease, to observe development of recurrent anastomotic inflammation and its relationship to mucosal phospholipase A2 (EC 3.1.1.4) activity. Ileal inflammation appeared soon after surgery in eight cases but in none of nine controls with noninflammatory bowel disease. The ileal inflammation was more severe 1-3 cm above than greater than 5 cm above the ileocolic junction (p less than 0.05), whereas the postanastomotic colonic mucosa remained unchanged. Ileal phospholipase A2 activity in the mucosa was equally raised at the two ileal sites (p less than 0.01 and less than 0.02), irrespective of the presence or absence of inflammation. In colonic postanastomotic mucosa the phospholipase A2 activity was the same as in the controls. Further followup showed preanastomotic ileal inflammation at both investigated levels in all patients with Crohn's disease but still with greater severity close to the mucosal junction (p less than 0.05). The study indicates that recurrent inflammation in Crohn's disease is initiated in the terminal ileum close to the ileocolic junction. Progression of severity is accompanied by greater proximal involvement. The increase in mucosal phospholipase A2 activity, which precedes endoscopically detectable inflammation, implies a role for this enzyme in Crohn's disease.


Pancreatic morphology and function in adult patients with cystic fibrosis.

To determine the relation between pancreatic morphology and pancreatic exocrine and endocrine function, we have studied 8 adult cystic fibrosis patients and 14 normal control subjects by ultrasonography and pancreatic function testing. In the patients with cystic fibrosis the maximum anteroposterior diameter of the pancreatic head was significantly increased over that in control subjects (p less than 0.01), whereas the maximum diameter of the body was significantly decreased (p = 0.05). Increased echogenicity of the pancreatic body was observed in most patients. In the cystic fibrosis patients postprandial insulin secretion was reduced in the 1st h (p less than 0.005 versus control), whereas pancreatic polypeptide secretion was virtually abolished for at least 3 h (p less than 0.01 versus control). All cystic fibrosis patients had evidence of exocrine pancreatic dysfunction as reflected by a diminished urinary para-aminobenzoic acid excretion. Intraduodenal enzyme and bicarbonate output in response to secretin-cholecystokinin was reduced in all of three patients studied. It is concluded that loss of endocrine and exocrine pancreatic function in adult cystic fibrosis patients is accompanied by a small and echo-dense pancreatic body relative to a large pancreatic head.


Postprandial gallbladder emptying is related to intestinal motility at the time of meal ingestion.

The characteristics of meal-induced gallbladder emptying in healthy individuals are subject to wide variation. We hypothesized that some of the observed variation might relate to ingestion of the meal during different phases of the migrating motor complex (MMC). Recording of gastrointestinal pressure was combined with scintigraphic recording of bile kinetics during infusion of 99mTc-HIDA. The material consisted of 12 healthy men. Group 1 (n = 6) had a fat-rich meal in phase I, and group 2 (n = 6) had the meal in a phase II. With the end of the meal ingestion as zero, the following results emerged. The subjects in group 1 had a median (range) lag period before beginning of gallbladder emptying of 13.5 (9.0-22.5) min. In group 2 gallbladder emptying began during the meal ingestion in four subjects, and the median lag period was 0 min (minimum, -9.0; maximum, 13.5 (p = 0.02)). The median percentage change of gallbladder counts during the observation period of 54 min in group 1 was 11.5% (from 19% filling to 25% emptying). The corresponding figures in group 2 were 41% (from 2% to 91% emptying (p less than 0.05)). This difference was due to the difference in duration of lag periods, as the emptying rates measured from the end of the lag periods were equal. In conclusion, the onset of postprandial gallbladder emptying relates to the phase activity of the MMC at the time of ingestion.


Antigliadin antibody, D-xylose, and cellobiose/mannitol permeability tests as indicators of mucosal damage in children with coeliac disease.

A dual sugar (cellobiose/mannitol) permeability test using an iso-osmolar solution was performed, to compare its ability to predict small-bowel mucosal damage in children affected by coeliac disease with the determination of serum levels of D-xylose and antigliadin antibody. Eighty-three children (67 on gluten-containing diet and 16 on gluten-free diet) were investigated. The D-xylose and the serum antigliadin antibody test predicted accurately 70% and 78% of the small-bowel biopsy results, respectively, whereas the cellobiose-mannitol permeability test predicted 93%. These data confirm the superiority of the permeability test over the D-xylose test, although the former cannot be advocated as a substitute for jejunal biopsy. Our results suggest a complementary use of the permeability test and the antigliadin antibody measurement as screening tests for coeliac disease before applying more invasive procedures.


Long-term results after 'floppy' Nissen/Rossetti fundoplication for gastroesophageal reflux disease.

Eighty-two patients (median age, 51 years; range, 27-87 years) with refractory gastroesophageal reflux disease (GERD) underwent floppy Nissen/Rossetti fundoplication during the period 1980 to 1990. The median postoperative hospital stay was 5 days (3-16). Median follow-up was 72 months and included endoscopy and a clinical and a questionnaire assessment. Subjective symptoms of reflux were abolished in 98%, and 96% of the patients were satisfied with the results. Endoscopy showed healing of the esophagitis in 98%. There had been no disruption of the fundoplication. Twenty patients complained of gaseous distention and increased flatulence; only two of them had severe problems. Three patients were unable to belch. In conclusion, the floppy fundoplication has been an effective operation with no deaths, a low incidence of morbidity and adverse side effects, and without a tendency for late failure.


Changes in the glutathione redox system during ischemia and reperfusion in rat liver.

After 60 min of reperfusion following 60 min of ischemia, the ischemia-induced decrease in liver tissue adenosine triphosphate (ATP) concentration had recovered by 66%, and full recovery of mitochondrial function--that is, the respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2)--was observed. In contrast, liver tissue ATP concentration had recovered by only 13%, and marked low RCI and ST III O2 were observed after 60 min of reperfusion following 180 min of ischemia. Intermediate results were observed in rats after 60 min of reperfusion following 120 min of ischemia. Liver tissue hypoxanthine and xanthine, substrates of xanthine oxidase, increased ischemic time dependently. Liver tissue concentrations of the reduced form of glutathione (GSH) and the oxidized form of glutathione (GSSG) and activities of glutathione peroxidase and glutathione reductase did not change after 60 min of reperfusion following 60 min of ischemia. In contrast, GSH concentration and glutathione peroxidase activity decreased significantly after 60 min of reperfusion following 180 min of ischemia. Since the glutathione redox system is an important contributor to the scavenging of free radicals after reperfusion following a long time of ischemia, the free radical scavenging ability might decrease in spite of enhancement of free radical generation, which might play an important role in the inhibition of the recovery of tissue ATP concentrations and mitochondrial function.


Hypoxaemia and myocardial ischaemia during and after endoscopic cholangiopancreatography: call for further studies.

Sixteen non-selected patients undergoing endoscopic cholangiopancreatography (ERCP) after diazepam premedication were monitored for oxygen saturation (SpO2) with a pulse oximeter and for myocardial ischaemia with a Holter tape recorder from 2 h before ERCP to 6 h after the procedure. One patient was excluded from data analysis because of oxygen therapy. Oxygen saturation was significantly decreased (p less than 0.05) both during endoscopy and in the postendoscopy recovery period. Heart rate was significantly increased (p less than 0.05) both during and after the procedure. ST depression occurred in no patients before endoscopy, in 10 patients during, and in no patients after endoscopy. Concurrent ischaemia and episodic hypoxaemia were found in 5 patients, isolated ischaemia in 7 patients, and isolated episodic hypoxaemia in 13 patients. Concurrent ischaemia and tachycardia were found in 10 patients, ischaemia without tachycardia in no patients, and isolated tachycardia in 1 patient. There was no significant correlation between diazepam dose and SpO2 during endoscopy. These results suggest tachycardia to be more important than hypoxaemia in the pathogenesis of myocardial ischaemia during upper gastrointestinal endoscopy. Cardioprotective measures other than oxygen therapy should soon be evaluated before the implications of the new standards of care in endoscopy have become generally adopted.


Is the irritable gut an inflamed gut?

Recent advances in the field of neuroimmunology have provided clear demonstrations of i) the neuromodulation of immune function, and ii) the involvement of the immune system in responses induced by psychologic stress in animals and in man. This has led to speculation about the role of the immune system in psychosocial disease. The irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction, which may reflect in altered motility, epithelial function, or sensory perception in the gut. IBS is heterogeneous not only in terms of its clinical presentation but also in terms of its pathogenesis, and factors ranging from psychoneurotic behavior and emotional stress, to dietary fiber deficiency, food intolerance, and enteric infection have been implicated. There is evidence of an increase in the inflammatory cells present in the gut of some IBS patients and in an emerging literature that demonstrates the immunomodulation of the motor system of the gut. These findings invite speculation that the immune system may play a role in the pathogenesis and pathophysiology of at least a subpopulation of IBS patients.


Idiopathic constipation: any movement?

Severe constipation now attracts considerable research interest. As a consequence, there have been recent advances in most aspects of this disorder. The epidemiology of this condition is now better appreciated, and subgroups of patients with different epidemiologies, symptom complexes, aetiologies, and treatments can now be distinguished. Radioisotopes enable detailed transit studies to be obtained of the entire gastrointestinal tract. Careful psychologic evaluation is an essential part of the evaluation. In young women with severe idiopathic constipation there is a decrease in propulsive mass movements, and specific colonic neurotransmitter abnormalities have been identified. Biofeedback therapy is an effective treatment for many of these patients. The variable results of surgery are now also clearly defined. Patients with chronic idiopathic intestinal pseudoobstruction can be categorized on the basis of their pathologic findings; detailed tissue studies may be required. The recognition that severe constipation encompasses various different conditions is leading to a more precise understanding of pathogenesis and treatment.


Inflammatory bowel disease: medical therapy revisited.

The chronic or recurrent immunologic and inflammatory response in ulcerative colitis and Crohn's disease may be initiated from the gut lumen. Deviation of gut contents away from the inflamed area, bowel rest, or the use of liquid diets appears to benefit Crohn's disease. The relative effects of complete bowel rest, or an elemental, hydrolysed, or polymeric liquid diet have not yet been established. Measures to alter the lumenal bacterial flora, including antibiotics, require further study. The use of corticosteroid drugs can be improved by the use of poorly absorbed or rapidly metabolized compounds. Amino-salicylates are effective in ulcerative colitis but require further study in Crohn's disease. Immunosuppressive drugs are valuable not only for a steroid sparing effect but also for control of chronic inflammation. New treatments designed to reduce inflammation are promising but will need to have high potency and an effect at the earliest stages of inflammation before a large number of different inflammatory mediators are released.


Nutritional support in inflammatory bowel disease: current status and future directions.

Malnutrition is a frequent occurrence in patients with acute inflammatory bowel disease. Total nutritional support provided either parentally (TPN) or enterally (TEN) has been advocated not only as an adjunct for improving nutrition but also as primary therapy. For patients with acute Crohn's disease, short-term rates of remission after TEN are equivalent to TPN. Coupled with certain advantages when compared with TPN, including simpler administration, fewer side effects, and preservation of the intestinal mucosal barrier, TEN may therefore be the preferred route for nutrient delivery. Controlled trials indicate equivalent or superior efficacy when enteral polymeric diets are compared with elemental diets for inducing remission in acute Crohn's disease. Moreover, when provided as an elemental diet, TEN is as effective as corticosteroids for achieving remission in acute Crohn's disease, but corticosteroids appear to be more effective than polymeric diets. Although the provision of nutritional support rather than bowel rest is the major factor contributing to symptomatic improvement, the optimal nutrient composition and the precise mechanisms whereby nutritional support achieves clinical remission remain to be clarified. In contrast to Crohn's disease, nutritional support is not effective for achieving remission in patients with ulcerative colitis. Thus, enteral nutritional support is an effective therapy for the short-term management of acute Crohn's disease. Whether long-term remission is equivalent to treatment with drugs or surgery requires prospective evaluation. Future avenues of investigation also include defining the optimal nutrient composition and the underlying mechanisms that achieve maximal nutritional repletion, promote mucosal cell renewal, and potentially directly retard production of inflammatory mediators.


Screening guidelines for colorectal cancer.

A review is given of methods and results of screening for colorectal cancer in average-risk and high-risk groups. Possible methods are digital rectal exploration, endoscopic examination, barium enemas, faecal occult blood tests, tumour markers like carcinoembryonic antigen, Ca-19-9, and others, and gene markers. Final results of large randomized population studies with faecal occult blood tests are expected within the next few years, but it will probably be necessary to add flexible sigmoidoscopy to achieve a major reduction in mortality from colorectal cancer in average-risk persons. Recommendations for screening in high-risk groups are proposed, but strong support for these guidelines are still missing, an exception being first-degree relatives of individuals with familial adenomatous polyposis; the other high-risk groups include members of hereditary non-polyposis colorectal cancer families, relatives of patients with sporadic colorectal cancer, patients with colorectal adenomas, patients with previous colorectal cancer, and patients with inflammatory bowel disease.


Laparoscopic gastrointestinal surgery.

The growth and scope of laparoscopic gastrointestinal surgery are outstripping the ability of medical journals to print series and reports of experience, and much data remain anectodal and preliminary. Laparoscopic cholecystectomy has become established, although, unfortunately, peroperative cholangiography has not yet become normal practice, despite convincing published evidence that it is likely to reduce the increased number of bile ducts that are damaged by laparoscopic surgeons. Imaging the bile ducts and the overall management of choledocholithiasis need re-evaluation, and the approach will change as more surgeons explore the bile ducts laparoscopically. Laparoscopic hiatal anti-reflux surgery will soon be routine, and a whole range of laparoscopically assisted operations on the oesophagus, colon, and rectum will become commonplace. Operations on the liver remain anecdotal. Throughout this rapid progress, surgeons must not forget the principles of (open) surgical practice, whilst carefully kept registers and regular audit of operations will provide new surgical standards.


Trefoil peptide expression in intestinal adaptation and renewal.

There are many avenues where molecular biology is important in studying the gut, and here we explore methods for defining expression of a new gene family in the gut. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide mRNA and peptide are expressed in the acinar and proximal duct cells, whereas pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed ectopically by goblet cells. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules. pS2 peptide was demonstrated in local neuroendocrine cells and was also co-packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We have also cloned the newest trefoil peptide intestinal trefoil factor from human and rat intestinal mucosa and shown its co-expression with mucus by normal intestinal goblet cells. The co-packaging of the same secretory protein in both mucous and neuroendocrine granules, which have different functions, is unusual and indicates an important role for pS2 in the secretory process itself or as a ligand delivered to its receptor via multiple routes. We conclude that the trefoil peptides are widely distributed in the intestine in inflammatory bowel disease and are of considerable potential functional importance.


New perspectives on acute pancreatitis.

The past decade has witnessed considerable changes in the clinical management of acute pancreatitis. Simultaneously, significant advances have been made in understanding the cellular and biochemical events involved in the initiation of this disease. This review summarizes recent clinical and scientific progress regarding acute pancreatitis and suggests areas for future investigation.


Non-steroidal anti-inflammatory drug gastropathy and cytoprotection: pathogenesis and mechanisms re-examined.

Gastric and intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) is a common and expensive adverse effect of this class of drugs. While it is likely that inhibition of prostaglandin synthesis by these agents is an important component of their ulcerogenic properties, the pathogenesis of NSAID gastropathy remains unclear. Likewise, the underlying mechanism for prostaglandin 'cytoprotection' is not fully understood, although it is clear from recent clinical trials that prostaglandin analogues are an effective treatment to prevent NSAID gastropathy. In this paper the contribution of neutrophils to the mucosal damage induced by NSAIDs is discussed, as is the possibility that prostaglandins protect the gastrointestinal mucosa from NSAID-induced ulceration at least in part through inhibitory effects on neutrophil function.


Primary biliary cirrhosis: new therapeutic directions.

The immunologic mechanisms responsible for the development of primary biliary cirrhosis (PBC) remain poorly defined, although recent investigations have provided new clues as to the role of cellular membrane proteins such as the mitochondrial autoantigens and intercellular adhesion molecules. Additionally, new therapeutic agents have become available that markedly enhance the prospect for medical management of both hepatic and extrahepatic manifestations of PBC. Definitive therapy with ursodeoxycholic acid and/or methotrexate, and symptomatic relief of pruritus with rifampicin or metronidazole may become standard in the years ahead. The results of their use to date in the treatment of PBC are detailed in this review. Successful therapy of hepatic osteodystrophy associated with PBC has yet to be achieved, although early data suggest a role for ursodeoxycholic acid, estrogen, calcium, and vitamin D in the management of this debilitating problem. Orthotopic liver transplantation continues to be successful for the management of advanced disease (greater than 70% 5-year survival) and will remain an essential therapeutic tool until definitive medical therapy for PBC becomes available.


Hepatitis C: what progress?

The new serologic assay for hepatitis C has made it possible to identify patients infected with this agent and to better characterize their clinical illness and its sequelae. As the clinical entity has become better recognized, our understanding of the infectious process has also progressed. Hepatitis C is a chloroform-sensitive RNA virus, only 30-60 nm in diameter, containing a lipid coat. Both erythrocytes and plasma can transmit infection. The viral genome consists of single-stranded linear RNA of approximately 10 kilobases. The first serologic assay developed was a radioimmunoassay, followed shortly by an enzyme-linked immunoassay. Secondary tests for specificity now exist. Blood donor populations may have a significant frequency of false positives on the antibody test, making it important that positive results be confirmed with a secondary assay. The antibody is only detected 2 months after infection, by means of currently available assays, and may not appear in many patients until 3 to 6 months after infection. Hepatitis C infection is commonly chronic. This may lead to an asymptomatic chronic carrier state without demonstrable liver disease, or to chronic progressive or non-progressive hepatitis.


Modern approach to alcoholic liver disease.

The pathogenesis of alcoholic liver disease is unclear. The recent literature on pathogenic factors, including direct effects of ethanol and its proximate metabolite acetaldehyde, associated nutritional factors, the formation of acetaldehyde-protein adducts, associated immune alterations, and the potential for liver injury due to coexisting hepatitis virus infection, is highlighted. The therapy of patients with advanced alcoholic liver injury, especially alcoholic hepatitis, is also controversial. It seems reasonable that all patients should receive adequate nutrition even if parenteral or enteral supplementation is required. Corticosteroid administration may benefit those patients with alcoholic hepatitis who have coexisting spontaneous hepatic encephalopathy and no gastrointestinal bleeding. For patients with complications from end-stage alcoholic cirrhosis, liver transplantation should be considered, as the patient with alcoholic cirrhosis does as well after liver transplantation as those patients with other forms of end-stage liver disease.


Issues in gastrointestinal endoscopy: oesophageal varices: inject, band, medicate, or operate.

Injection sclerotherapy is the most widely used definitive treatment of acute variceal bleeding and is increasingly performed at the time of the first emergency endoscopy. Direct endoscopic ligation of varices by banding is a new technique under evaluation for both acute bleeding varices and long-term management. Repeated injection sclerotherapy is one of the major options for long-term management after variceal bleeding. More major surgical procedures are usually reserved for the failures of sclerotherapy in the management of acute variceal bleeding, whereas portosystemic shunts, particularly the distal splenorenal shunt, or an extensive devascularization and transection operation are commonly used alternative forms of therapy in long-term management. All patients with variceal bleeding should be assessed for liver transplantation, although only a few will ultimately receive a liver transplant. Medication with propranolol is widely recommended in long-term management, but its use in this context remains controversial. The most controversial area of management is prophylactic treatment before variceal bleeding. Major surgical procedures and injection sclerotherapy are not justified at present because it is difficult to identify those patients with a high likelihood of a first variceal bleed. Although medical therapy with propranolol has proved the most successful therapy to date, a case is made for treating most patients conservatively until their first variceal bleed occurs or until better predictive indices for patients at high risk of a first bleed are identified.


Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'.

This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment.


Endoscopic ultrasonography.

Endoscopic ultrasonography (ES) enables accurate imaging of the layering structures of the gastrointestinal tract. The equipment is still evolving but has already reached a high degree of sophistication. The most relevant clinical indications are the analysis of submucosal tumors, the imaging of intestinal vascular anomalies, and, especially, the staging of gastrointestinal and biliopancreatic malignancy and the monitoring of the therapeutic efficacy of surgery, Nd:Yag laser photodestruction, and radiotherapy.


Laser therapy: more smoke than light?

Lasers have been used endoscopically in the management of gastrointestinal (GI) diseases for 15 years. Although the initial use was for therapy of GI bleeding, other more portable less expensive modalities have supplanted the laser in this area. Currently, its primary application is for therapy of GI neoplasms. If lasers are to be used with increased frequency, it will require that its unique property--selective absorption--be more of a focus than simply using it as a thermal device. Pigmented vascular lesions such as angioma or watermelon stomach are ideally suited for laser therapy using a wavelength preferentially absorbed by hemoglobin. The future use of lasers for gastrointestinal diseases--both diagnostically and therapeutically--will depend on taking advantage of this unique characteristic of laser light.


Nonsteroidal anti-inflammatory drugs--the clinical dilemmas.

Physicians using nonsteroidal anti-inflammatory drugs (NSAIDs) are concerned that effective anti-inflammatory doses cause few gastrointestinal side effects. Among the causes of discontinuing therapy, upper gastrointestinal symptoms and the development of 'ulcer' complications are major concerns; endoscopic findings in asymptomatic users are not. Initial symptoms, poorly correlated with endoscopic findings, are relieved by anti-ulcer drugs and ameliorate with time of NSAID use in most patients. Symptoms accompanied by epigastric tenderness, or unrelieved by H2 antagonists, or resulting in cessation of NSAID therapy are more predictive of underlying ulcers. Complications probably arise in several ways, including as hemorrhages due to interference with platelet function, and as complications due to exacerbations of underlying ulcer disease or of ulcers caused by the NSAIDs. Pathogenesis and effective prophylaxis (yet to be established) may therefore vary in different patients, a clinical dilemma.


Infection and endoscopy: who infects whom?

Infection is one of the major hazards of endoscopic procedures and is the commonest complication of endoscopic retrograde cholangio-pancreatography (ERCP) causing death. Prevention of endoscopy-associated infections is based on adequate cleaning and disinfection regimens. Scrupulous mechanical cleaning is fundamental; even prolonged chemical disinfection will be ineffective if cleaning has not been adequate. Special measures are required to prevent ERCP-related infections. It is important to recognize various special circumstances that increase a patient's susceptibility to infection and to administer antibiotic prophylaxis when appropriate.


Asleep on the job: sedation and monitoring during endoscopy.

Gastrointestinal endoscopic procedures are invasive and carry a significant morbidity and mortality, even for diagnostic procedures (mortality of 1 in 2000 for upper gastrointestinal endoscopy). The commonest causes of death are cardiopulmonary complications, which may in part be related to sedative techniques. The clinical end-points for sedation need to be reappraised and should aim to induce amnesia rather than hypnosis. Endoscopists need to be familiar with the pharmacokinetic and pharmacodynamic properties of the benzodiazepines used for sedation. This applies particularly to the protracted half-lives of some benzodiazepines and the major drug interaction with significant synergy that occurs if opioids are used in combination with benzodiazepines. Thus appropriate doses of these drugs should be administered. The use of supplemental oxygen and pulse oximetry, combined with continuous intravenous access during the procedure should be standard practice. Endoscopists should be aware of national guidelines for safe endoscopic practice.


Effect of mucosal and systemic immunization with pneumococcal polysaccharide type 3, 4 and 14 in the rat.

Four immunization routes were investigated to induce an immune response against three structurally different types of pneumoccoccal polysaccharide (PPS) in the rat. In particular, the contribution of the IgA isotype in these immune responses was studied. Six days after administration of PPS type 3, 4 or 14, the localization of specific antibody-containing cells (ACC) in different lymphoid tissues and the antibody titres in serum were studied. All four routes induced anti-PPS ACC in the spleen. After intraduodenal, intravenous and especially intraperitoneal administration of PPS, many IgA-specific anti-PPS ACC were also found in parathymic and mesenteric lymph nodes and in the lamina propria of intestinal tissue. Several anti-PPS ACC were found in Peyer's patches, located peripheral of the B-cell areas. The intratracheal immunization elicited only a local immune response, in bronchus-associated lymphoid tissues and paratracheal lymph nodes. The localization of these anti-PPS ACC was influenced by the route of immunization. After all four investigated routes, specific antibodies were found in serum against PPS. However, some remarkable differences between PPS-3, 4 and 14 were found in the magnitude of the immune response and the distribution of the isotypes. Both route of immunization and structure of the PPS have a profound influence on the immune responses in rats.


T-cell receptor V-gene usage in synovial fluid and synovial tissue from RA patients.

The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly, evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V-gene expression within an inflammatory lesion may require separate analysis of the two T-cell subsets. In this paper we have therefore studied T-cell receptor V-gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti-TCR monoclonal antibodies and antibodies to CD4 and CD8, respectively. Double stainings were also performed with anti-TCR antibodies and antibodies to activation markers HLA-DR and IL-2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T-cell populations, but no uniform pattern was evident among the 35 patients investigated.


Isoelectrophoretic characterization of protein antigens present in mycobacterial culture filtrates and recognized by monoclonal antibodies directed against the Mycobacterium bovis BCG antigen 85 complex.

Nine monoclonal antibodies (MoAbs) were produced against Mycobacterium bovis BCG antigen 85 complex. Using isoelectric focusing combined with Western (immunoblot) blot analysis, antigenically related proteins could be identified in culture filtrates from M. tuberculosis, M. bovis, M. Kansasii, M. avium, M. xenopi, M. gordonae, M. fortuitum, M. phlei and M. smegmatis. Most of the MoAbs were found to be broadly cross-reactive between the various mycobacterial species, albeit some minor differences were observed. These MoAbs reacted generally, in each species, with different components. One MoAb (VID1-14) was found to be specifically directed only against antigen 85B from M. bovis, M. tuberculosis and M. kansasii.


Analysis of the genomic and derived protein structure of a novel human serum amyloid A gene, SAA4.

We have determined the structure of the novel SAA gene, SAA4. The gene is 6.2 kb in length and comprises three introns and four exons. Introns 2 and 3 are significantly longer than those of the other human SAA genes. We have sequenced the exons and junction fragments and have shown that the sequence is the same as c-SAA[1] and does not correspond to the pseudogene carried on GSAA4[2]. The predicted SAA4 protein sequence has an eight amino acid insertion relative to the other human SAA proteins and is more closely related to rabbit and mouse SAA proteins than to the other human SAA proteins, or to those of animal species which also possess an insertion. We have analysed the predicted SAA4 protein relative to the other human SAA proteins and have identified three important structural regions. We predict that region 1 of SAA4 represents a lipid binding domain. Region 2 forms an extensive, distinctive, hydrophobic beta sheet region in place of a helical region. In region 3, SAA4 is the only SAA protein having an alpha helix which is not amphipathic. We predict that the SAA4 protein retains a modified function of the conserved region, retains the Ca2+ binding site, has an amino terminal surface site and has a potentially distinct secretion pattern. Together, these differences indicate a distinct function from those of the other SAA proteins.


The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice.

The main conclusions of this study are that BCG/PPD-activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA-induced production of H2O2, kill about one-third of the phagocytosed Candida albicans, and cause more than 50% inhibition of the intracellular formation of germ tubes by C. albicans. Peritoneal macrophages from mice that were colonized post-natally with C. albicans do not show increased production of H2O2 upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree. These macrophages are capable of killing about 20% of the ingested C. albicans. In vivo, the number of Candida in the kidney, spleen and liver after intravenous injection of Candida albicans is significantly lower in BCG-treated mice than in control mice. Post-natal colonization with C. albicans has only a limited effect on the outgrowth of intravenously injected C. albicans in the spleen and liver but does not influence growth in the kidney. These results indicate that acquired immunity against a systemic Candida infection involves both oxidative and non-oxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of C. albicans.


The effect of disodium cromoglycate on in vitro proliferation of peripheral blood mononuclear cells from allergic and healthy donors.

The effect of disodium cromoglycate on in vitro proliferative responses of peripheral blood mononuclear cells from healthy individuals, allergic patients with moderate serum IgE and patients with atopic dermatitis and high levels of serum IgE was investigated. Peripheral blood mononuclear cells were stimulated with mitogens (phytohaemagglutinin, Concanavalin A), recombinant interleukin-2, calcium ionophore + phorbol 12-myristate 13-acetate, purified protein derivative of tuberculin and allergens. It was possible to induce in vitro specific, allergen-triggered responses only in allergic individuals with moderate serum IgE and not in individuals with atopic dermatitis and high serum IgE. Generally, whenever the stimulatory signal(s) caused a significant proliferative response, disodium cromoglycate inhibited the proliferation. This inhibition was seen for all activation agents and for both healthy and allergic individuals. By contrast, for certain non- or low-responders (both healthy and allergic individuals) disodium cromoglycate seemed to amplify the proliferation to various activation signals. Only non- or low-responder cells derived from atopic dermatitis patients showed a biphasic kinetic response pattern when stimulated with the drug in combination with recombinant interleukin-2, recombinant interleukin-2 + ionophore or specific allergens.


Antigen-activated T cells inhibit cartilage proteoglycan synthesis independently of T-cell proliferation.

Previously we have shown that blood mononuclear cells (MNC) obtained from patients with rheumatoid arthritis (RA) have the capacity to induce depletion of proteoglycans (PG) in human cartilage explants. This was observed especially after stimulating MNC with mycobacterial antigens, rather than with the mitogen Concanavalin A (Con A). We have now co-cultured cartilage explants in the presence of T-cell clone A2b obtained from the rat model of adjuvant arthritis (AA). We show that inhibition of the cartilage PG synthesis is a consequence of antigen-specific T-cell activation and that it is mediated by a humoral factor. This seems to be a cytokine rather than an enzyme. Moreover, at the level of polyclonally responding T cells, inhibition of PG synthesis due to T-cell activation by mycobacterial antigens was shown to depend on prior mycobacterial immunization. Arthritogenic T-cell clone A2b also showed PG synthesis inhibitory effects when co-cultured with cartilage alone. The inhibitory activity was shown to be unrelated to the degree of T-cell proliferation. We conclude that antigen-specific T-cell activation may be one of the initiating events leading to cartilage damage in arthritic processes. The measurement of T-cell-mediated PG synthesis inhibition may be a more sensitive and relevant assay for the detection of pathogenic T cells than T-cell proliferation.


OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction.

The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G-CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression.


[Pathomorphology of damaged cerebral microcirculation after global ischemia in the dog. Study of the cortical ectosylvian rostral gyrus].

Pathological-morphological changes in the brain microcirculatory blood vessel in dog after global brain ischemia have been evaluated qualitatively. In series of cut sections thick 200 microns dyed with benzidine, a marked microthrombotization of the brain capillaries without vasostasis as well as cylindrical microthrombi and microthrombi with vasostasis were observed. The described light microscopic angioarchitectonic findings account for the phenomenon of vasomotoric paralysis.


[A model of mild spinal cord injury in rats--dynamics of changes in motor function].

Authors proceeded by performing compressive spinal traumas of variable intensity in 21 rats at lower thoracic level over an intact dura. The deficit of hind limbs motor functions was evaluated simultaneously with the two tests as follows: a) in observing the gait of an animal along with graduation in accord with modified Tarlov's classification, b) with the method of inclined plane. The reproducibility of injuries of various intensity appeared to be imperfect. Five animals with severe injury died up to 4 weeks (Fig. 4, 5). The remainder of them showed substantial approval (mild injury--Fig. 6-13). The dynamics of motor disorder showed changes up to 6 weeks, after then the state persisted unchanged up to 2 months. Within this survival interval, rats were killed either in the state of mild paresis or even under regained normal condition. It outflowed from our study that a long term monitoring of postinjury spinal cord function is important in order not to ascribe possible approval of the functions to the therapy applied. Further on course of disorder can be predicted in accordance with duration of initial paraplegia. The post-surgery paraplegia had lasted for only several hours in the animals whose injuries resulted in a normal condition.


[Non-contact experimental burns in rats].

Both healthy female rats of the Wistar strain (VELAZ breed) and those irradiated with a single whole-body dose of 5 Gy gamma radiation (60Co) were exposed on the back to non-contact infrared radiation (IR lamp with an output of 250 W: skin surface temperature at a distance of 3 cm from the crown of the lamp = magnitude of 110 +/- 2 degrees C) for time periods of 40 s, 20 s, 10 s (healthy) and 20 s (irradiated animals). The surface range of thermic damage to the skin was determined using planimetry and measuring the length and the width of the burn with the respect to an immediate contraction. The mean values of an immediate retraction of the burnt skin and the interval of reliability of their estimate (p < 0.05) were significantly lower in 10 s exposure and in whole-body irradiation rats after 20 s (magnitude of 5.6 +/- 2.5 % ... 10 s; magnitude of 12.56 +/- 3.86 % ... in irradiated animals) than the retraction of non-irradiated rats (magnitude of 15.98 +/- 4.86 % ... in 20 s; magnitude of 31.88 +/- 7.34 % ... in 40 s). For a period of 90 min after burning, no substantial changes were found in rectal temperature (33.4 degrees C to 35.4 degrees C). Before a thermic trauma the drop in the temperature from the skin surface reached cca 2 degrees C subcutaneously, after burning in the centre of the burn about 17 degrees C and 9 degrees C in other exposures using the IR lamp. The mean time of burn healing in non-irradiated animals was the shortest in 10 s exposure (magnitude of 17 +/- 2 days), the damage in the centre reaching II b degree while after 40 s exposure the burn reached IV degree and also the longest healing time (magnitude of 60 +/- 4 days). After 20 s exposure, the mean healing times in irradiated rats were longer (magnitude of 39 +/- 3) days and so the skin damage (III to IV degree) as compared with non-irradiated animals where the mean healing time amounted to (34 +/- 4) days, the burns being of III degree.


[Induced cell fusion in a heteroploid cell line].

Non-uniformity in properties of the cells within the stabilized heterocaryonic line is certified by the decrease in capacity of the cells to fuse together after repeated influence of polyethylene glycol. Multiple and large polycaryonic formations resulting from primary administration of fusogen are relatively rapid in extinction. The cells having been survived after repeated administration of polyethylene glycol appear to fuse predominantly into less extended polycaryocytes with smaller multiplicity. This fact may be a consequence of the selection of a portion of non-uniform cell population being more susceptible to this fusogen. Those concerned are probably the cells rather different in surface qualities and/or adjacent parts of cytoskeleton.


[The therapeutic effect of diazepam in dichlorvos poisoning].

In order to study the influence of diazepam on both cholinergistic and non-cholinergistic (stressogenic) effects of phosphororganic insecticide dichlorovos, both the activity of cholinesterase in selected organs and blood as well as biochemical markers of stress (plasma corticosterone, tyrosine aminotransferase activity in the liver) have been applied. Comparing the course of diazepam-treated and untreated dichlorovos intoxication, cholinesterases showed greater increase in inhibition in the first case. There was smaller decrease in activity of acetylcholinesterase in CNS and diaphragm compared with untreated intoxication. Although the changes of plasma corticosterone level were entirely corresponding to those of untreated intoxication, there was still greater increase in activity of tyrosine aminotransferase when compared with untreated intoxication. A marked increase in activity of tyrosine aminotransferase is more convenient for an intoxicated organism, because tyrosine aminotransferase stimulates gluconeogenesis. Even in absence of a complete elimination of cholinergistic and stressogenic effects of dichlorovos, diazepam, as a drug, influenced markedly their course. Thus its significance of component of a complexive atropine-oxime therapy of the intoxication with organophosphates appears to be undiscussible and wider than stressed usually.


[Literature findings and suggestions for modification of the fluorometric method for determination of n-acetyl-beta-d-glucosaminidase in urine].

Literature data are summarized on the determination of N-acetyl-beta-D-glucosaminidase (NAG) in human urea. Based on these data, the modified determination of NAG activity in urea has been worked out. The latter consists in selection of suitable conditions for providing enzyme reaction and conditioning the area sample used to determine the NAG activity.


[Evaluation of the kinetics of the left ventricular wall using the Cardio 200 computer].

The WALLMO program was used in comparing normal kinetic values of left ventricle wall with those obtained from control patients and literature sources. Authors concluded that, when based on the original data for RAO projection, the evaluation of regional LV wall contractility gives erroneous results in estimating whether a given section is normo- hypo- or hyperkinetic. Therefore, the set of normal kinetic values of LV motion has been formed for individual numbers of radials. This set may be used also at other working sites.


[The carcinogenicity of gasoline (review of the literature)].

In accord with new findings, the gasoline is no more believed to be free of cancerogenic risk. Renal tumours in male rats and those of liver in murine females had been described also after inhalatory exposure to unleaded gasoline. A reliable epidemiological study in occupationally gasoline exposed humans is still not available (higher rate of tumours in workers of chemical petrol processing industry due to the influence of gasoline appears to be an indirect proof, because apart from gasoline also other substances are involved simultaneously). With regard to a mechanism of action, those first published have been the negative results of testing for chromosomal abnormalities and bacterial genetic mutations. However, the mutagenicity was proved further on molecular level with the use of appropriate tests (e. g. induction of DNA repair synthesis). Certain authors ascribe more importance to the promotional rather than initiational effect of gasoline. However, the former is not accentuated by the IARC. Further studies should be predominantly based on molecular genetic approaches and epidemiological studies.


[Comparison of the quality of diagnostic approaches using the characteristic (ROC) curve test].

The method is described to compare the quality of two diagnostic approaches as based on comparing surfaces under the ROC test curve. Apart from small deviations, this method may be applied on independent samples and paired observations carried on identical individuals. Experimental data are issued from comparing two methods of prediction of the survival in dogs on the radiobiologic experiment.


Clinical background of patients treated with clean intermittent catheterization in Norway.

This study reports on the use of clean intermittent catheterization (CIC) in Norway in 1988/89. A total of 407 adult out-patients was studied. CIC was used in all age-groups and equally in both sex. The patients were divided into five diagnostic groups. There were twice as many patients suffering from neurogenic diseases as non-neurogenic ones. A neurourological index was constructed based on neurological examination and urodynamic data giving a good differentiation and expression of the bladder affection. It appeared that CIC could be performed even by highly disabled persons. A statistically significant correlation was found between the neuro-urological results in patients with decompensated bladder and their over all disability.


Autotransposition of vas in a 2-stage procedure. An experimental study in the rat.

The patency rate of vasovasostomy in autotransposed vas has been studied using a technique set up in a rat model. In a two-stage procedure, 1 cm of the vas deferens was transposed to the opposite side. The anastomoses were performed with a simplified microsurgical suturing technique. On final examination, 9 of 15 rats operated upon showed good sperm passage over the transposed vas segment. Sperm granulomas were recorded in four of fifteen cases. Sperm antibodies were demonstrated in eight of fifteen cases.


Radical retropubic prostatectomy: our experience with the first 54 patients.

Complications were analysed in a contemporary series of the first 54 retropubic radical prostatectomies performed for carcinoma of the prostate at our Institution. The postoperative morbidity was notable; three life threatening and ten minor complications occurred within the first 30 postoperative days. Thus, more than 1 year after the operations 7 patients had severe stress incontinence and 17 noticed minor degree of incontinence. Twenty-six per cent of the patients who claimed to be potent before surgery maintained potency. The operative time averaged 195 min and the demand for transfusions averaged 2.98 units per patient. Our experience in this early series of radical prostatectomy is that the operation cannot be done without notable postoperative morbidity.


The muscularis mucosae of the human urinary bladder. Implications for tumor staging on biopsies.

The human urinary bladder wall is traditionally described as being without a muscularis mucosae. A consecutive one year material of 772 bladder biopsies from 171 patients were examined for the proposed presence of lamina muscularis mucosae (MM). MM was observed in 15% of the biopsies and in 35% of the patients and graded into three patterns according to its continuity. Biopsies with transitional cell carcinomas were reviewed in order to find out whether MM-positive biopsies had been staged correctly. The data are discussed in relation to earlier studies on the subject.


Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial.

To evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients.


Technique of renal biopsy by ultrasound guided percutaneous puncture with a spring loaded "gun".

The study consisted of 89 consecutive patients (mean age = 41.5, range = 16-82, 64 men, 25 women) referred for renal biopsy because of clinical suspicion of renal parenchymal disease. Neither transplant kidneys nor tumour evaluation were included. A biopsy "gun" (Biopty) and 14 (2.0 mm) and 18 (1.2 mm) gauge needles were used with ultrasound guidance. Sixtyseven renal biopsies were guided using a freehand technique 42 using a fixed angle guide attachment. The mean glomerular yield was 9.4 glomeruli. Almost 25% of the 18 gauge needle biopsies (n = 57) had to be repeated and 29.3% of the 14 gauge needle biopsies (n = 75). The yield difference was not statistically significant (Chi-squared = 0.37, p = 0.54). There was no statistically significant difference between the distributions of failure to obtain a significant material for evaluation caused by the biopsy technique used (Chi-squared = 0.08, p = 0.78). When analysing cases of single successful pass the thinner needle produced 6.7 glomeruli (n = 36, SD = 5.08) and the thicker needle 13.8 glomeruli (n = 18, SD = 6.82). No serious complications occurred.


Microalbuminuria in obesity.

Albumin excretion rate, glomerular filtration rate (GFR) and kidney volume in obese patients and normal-weight controls were compared with body mass index (weight (kg)/height2 (m)) in 17 subjects. Body mass index varied from 21.5 to 48.0, the albumin excretion rate from 2.8 to 17.8 micrograms/min, and the kidney volume from 238 to 468 ml. Body mass index correlated significantly with albumin excretion rate and with kidney volume (p < 0.01), but not with the GFR. Neither the body mass index nor the albumin excretion rate showed any correlation with blood pressure. Albumin excretion rate in obese subjects could be as good an early predictor of complications as it is in patients with diabetes mellitus, and in the elderly.


Pretransplant parathyroidectomy in renal failure: effects on bone histology and aluminum deposits during dialysis and after kidney transplantation.

Using repeat bone biopsies, we studied whether 1) subtotal parathyroidectomy (PTX) enhances aluminum (Al) deposition in bone and 2) whether pretransplant PTX affects Al removal from bone after kidney transplantation. Twenty-four kidney graft recipients, 10 subjected to PTX 9-44 months prior to transplantation and 14 controls matched for dialysis duration, had bone biopsies taken at transplantation. Serum calcium and parathyroid hormone levels had decreased after PTX in all 10. At transplantation, eroded bone surface was lower in PTX-recipients, while extent of Al-stained bone surface and prevalence of symptomatic Al-related bone disease were similar in both groups (PTX: 2/10; non-PTX: 4/14). Hence, PTX did not enhance accumulation of stainable bone Al nor increase prevalence of clinical bone disease during dialysis. Fourteen (7 PTX) recipients with functioning grafts had a second biopsy 12 months after transplantation. Symptomatic Al-related bone disease was cured regardless of pretransplant PTX, and Al-stained surface had decreased in all but one (PTX) recipient.


The impact of total unilateral ureteral obstruction on intrarenal angiotensin II production in the polycalyceal pig kidney.

Nine pigs with unilateral complete ureteral obstruction were investigated for 15 hours. Obstruction of the ureter resulted in a maximum intrapelvic pressure of 60 cmH2O within the first hour after obstruction, and a gradual decline to 40 cmH2O during the next 15 hours. In 6 pigs both renal veins were catheterized together with the abdominal aorta allowing measurement of the hormonal difference over the kidney. Plasma angiotensin II, plasma vasopressin and plasma atrial natriuretic peptide concentrations were determined. Arterial concentration of plasma angiotensin II gradually increased from 38.7 pg/ml to 252.3 pg/ml. The highest concentrations of angiotensin II were found from the ipsilateral renal vein. From 1 hour after obstruction and onward there was a negative extraction ratio of angiotensin II from the ipsilateral kidney indicating enhanced intrarenal generation of angiotensin II. No difference in vasopressin was found among the sample sites, but a significant reduction in vasopressin from 15.2 pg/ml to 4.9 pg/ml was found from the ipsilateral renal vein during the 15 hours of unilateral ureteral obstruction. Arterial atrial natriuretic peptide concentrations were higher than renal venous levels at all times. Glomerular filtration was immediately reduced to 58%. It is suggested that an increased ipsilateral generation of intrarenal angiotensin II is at least partly responsible for some of the changes in kidney function during acute obstruction.


Bilateral epididymal sarcoidosis. Case report.

A 59-year-old man presented with a four-month history of almost painless bilateral scrotal swellings. Histological examination of a biopsy specimen confirmed sarcoidosis. He was well two months later, the mass had not increased, and he was receiving no treatment. This is the nineteenth reported case to our knowledge, and the eighth with bilateral disease.


Uretero-iliac fistula--a rare cause of hematuria. Case report.

Fistulation between the ureter and iliac artery is a rare cause of hematuria. Like our case, most of the cases reported so far, originate from traumatic or iatrogenic lesions. This condition should be considered in patients with massive hematuria and underlying predisposing factors.


Changes in renal function during the development of hypertension and effects of antihypertensive treatment. A case report.

Renal function was serially investigated during the development of hypertension in a 12.8-year-old girl with chronic glomerulonephritis. Clearances of inulin (CIn) and para-aminohippuric acid (CPAH), filtration fraction, and sodium excretion were measured during hydropenia and isotonic saline volume expansion. Blood pressure was initially labile, but after a few years fixed hypertension developed, and antihypertensive treatment with propranolol was started. During the early stages of hypertension, the filtration fraction during hydropenia was reduced, but the natriuresis during volume expansion was normal. When the hypertension was fixed, glomerular filtration rate, CPAH, and filtration fraction were normal, but the natriuresis was exaggerated. Antihypertensive treatment only partially corrected the natriuresis.


Phaeochromocytoma--an unusual cause of haematuria.

A patient was admitted to hospital because of haematuria. A papillomatous bladder tumor was removed. Histological examination revealed a phaeochromocytoma. Fourteen days postoperatively the urinary excretion rates of catecholamines were elevated but normalized afterwards. Abdominal computed tomography and metaiodobenzylguanidine scintigraphy were normal. No hypertension or characteristic micturitional attacks preceded removal of the tumor.


Diagnostic criteria in schizophrenia: accentuate the positive.

In a recent article, Andreasen and Flaum (Schizophrenia Bulletin, Vol. 17, No. 1, 1991) argued that greater emphasis should be placed on negative symptoms in the diagnosis of schizophrenia, leading to a less important role for positive symptoms. This article presents a counter-argument to this view. Positive symptoms are common and reliable and therefore highly useful diagnostically. First-rank symptoms, although not specific to schizophrenia, show good discriminability. No other type of symptom or investigative method can make such claims to usefulness. Although positive symptoms do not predict outcome, this is not a necessary function of diagnostic criteria. The predictive power of negative symptoms is, in any case, based largely on studies of patients with chronic disorder. Premorbidly impaired social development may interact with schizophrenia, worsening the prognosis. We believe positive symptoms have always been the essence of psychiatric disorder and should remain so. Increasing the diagnostic weight given to negative symptoms risks restricting the definition of schizophrenia excessively.


Disorder of attention in individuals with schizotypal personality.

This study was designed to examine disorder of switching attention in normal individuals with schizotypal personality. High scorers on the physical anhedonia (PA) and schizophrenism (SZ) scales of a questionnaire constructed to measure schizotypy were compared with a group of control subjects. A reaction time test was used that required switching attention across or between auditory and visual modalities. It was found that the high PA scores and the high SZ scorers showed a deficit of shifting attention across modalities compared with the control subjects.


The efficacy of Arthrotec in the treatment of osteoarthritis.

In a double-blind study, 455 patients with osteoarthritis were randomly assigned to receive a combination of Arthrotec, 50 mg of diclofenac and 200 micrograms of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 4 weeks. At weeks 2 and 4 of treatment, no significant differences between the treatment groups were noted in changes from baseline on the physicians' and patients' global assessment of osteoarthritis. On a measure of arthritis severity, patients with both arthritis of the hip and knee showed improvement from week 2 to week 4, with no significant differences between treatment groups.


The safety of Arthrotec in patients with rheumatoid arthritis or osteoarthritis: an assessment of the upper gastrointestinal tract by endoscopy.

Two double-blind comparative studies were conducted to determine the upper gastrointestinal safety of Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol versus 50 mg of diclofenac. In one study, rheumatoid arthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 12 weeks. Endoscopy was performed before and after treatment. At the termination of treatment, among the 290 patients with rheumatoid arthritis, gastroduodenal ulcers were found in 4% of the Arthrotec-treated patients and in 11% of the diclofenac-treated patients (P = 0.034). In the second study, osteoarthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 4 weeks. Endoscopy was performed before and after treatment. Among the 329 patients with osteoarthritis, gastroduodenal ulcers were found in none of the Arthrotec patients and in 4% of the diclofenac patients (P = 0.015).


Overall safety of Arthrotec.

Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol-treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups.


Biopharmaceutical profile of diclofenac-misoprostol combination tablet, Arthrotec.

Arthrotec, a combination tablet has been developed that contains 50 mg of diclofenac in an inner core and 200 micrograms of misoprostol in an outer mantle. Both diclofenac and misoprostol are extensively absorbed and their maximum plasma concentrations, but not total availability, are diminished when taken with food. Both drugs have elimination half-lives of less than 2 hours and do not accumulate in plasma after recommended doses. Pharmacokinetic and bioavailability studies of the combination product taken separately and together reveal a high between- and within-subject variability in plasma diclofenac levels, especially when the enteric-coated tablets were given after food; reliable values for peak plasma diclofenac concentration could not be ascertained. No pharmacokinetic interactions between diclofenac and misoprostol were apparent. The bioavailability of diclofenac and misoprostol from the combination tablet was similar to that seen when the two drugs are given separately.


The economic consequences of NSAID-induced gastropathy: the French context.

The costs of treating gastroduodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are shown to increase the total cost of NSAID treatment to the Assurance-Maladie, the French national health insurance system. This increased cost is termed the iatrogenic cost factor, and is defined as the ratio of the shadow price of an NSAID to its reimbursed cost. The shadow price is calculated from estimates of the incidence of NSAID-induced gastropathies, the cost of the drug, and the hospital and ambulatory costs of treating the gastropathies. The resulting iatrogenic cost factors are estimated as 1.36 for naproxen, 1.48 for sulindac, 1.65 for diclofenac, 1.67 for piroxicam, 2.00 for ketoprofen, and 2.12 for etodolac.


The economic consequences of NSAID-induced gastropathy in the United Kingdom and commentary on the article by G. de Pouvourville.

The iatrogenic cost factor of treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is defined as the increase in cost resulting from NSAID-induced gastroduodenal ulcers. The iatrogenic cost factor of NSAIDs for the National Health Service (NHS) in the United Kingdom was calculated using the model of de Pouvourville (1992). The cost factor is defined as the ratio of the shadow price of the NSAID to the NHS price. The shadow price is calculated from the incidence of NSAID-induced gastroduodenal ulcers and the costs of treating them and the price of the drugs. The NHS iatrogenic cost factors of 10 NSAIDs were similar to those calculated by de Pouvourville for the French national health insurance system, Assurance-Maladie, and ranged from 1.08 for diclofenac/misoprostol to 2.38 for ibuprofen.


Efficacy of Arthrotec in the treatment of rheumatoid arthritis.

In a double-blind study, 346 patients with active rheumatoid arthritis were randomly assigned to receive Arthrotec, a combination of 50 mg of diclofenac and 200 *g of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 12 weeks. At weeks 4, 8, and 12 of treatment, no clinically significant differences between the two treatment groups were noted on measures of joint tenderness, pain, and swelling or on physicians' and patients' assessments of disease severity.


Endothelial cell destruction by polymorphonuclear leukocytes incubated with sera from patients with systemic lupus erythematosus (SLE).

When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti-EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease.


Morphological evidence for biological control of urate crystal formation in vivo and in vitro.

Urate crystal formation, and subsequent gout, occurs in only a minority of hyperuricaemic subjects indicating that factors other than hyperuricaemia are involved. Biological substances (especially proteins) alter crystal growth in vitro independently of uric acid concentration. Physiological crystal formation, known to be under biological control, is characterised morphologically by uniformity of size and constraint of crystal shape. To determine whether pathological urate crystal formation is influenced by the surrounding biological milieu we examined, using scanning electron microscopy, the morphology of urate crystals formed either in vivo or in vitro. We found morphological evidence of biological control of in vivo urate crystal formation and demonstrated that those characteristics could be induced in vitro by the addition of serum, synovial fluid and certain serum proteins to the growth medium during crystal formation. Urate crystal formation is dependent, not only on the degree of hyperuricaemia, but also on the surrounding biological milieu.


Nailfold capillary permeability in psoriatic arthritis.

This study is the first report of the permeability status of nailfold capillaries in psoriatic arthritis (PA). "Traditional" nailfold capillary microscopy and intravital fluorescence videomicroscopy were carried out at the nailfold of 13 patients with PA. Twenty five healthy subjects served as controls for nailfold capillary microscopy, and 15 out of these for fluorescence videomicroscopy. The following parameters were assessed: capillary length, apex width, maximum loop width, maximum limb width, loop density, visibility of subpapillary venular plexus, loop tortuosity, transcapillary diffusion, and interstitial concentration at different sites and times of Na-fluorescein given in intravenous bolus. Morphometric analysis of capillaroscopic findings showed a significant increase of loop length (mean +/- SD: 290.1 +/- 73.5 microns) when compared to healthy controls (223.3 +/- 51.9 microns) (P < 0.02). Transcapillary passage of Na-fluorescein was homogeneous and symmetric both in PA patients and in controls. Mean transcapillary and interstitial diffusion was not significantly enhanced at the nailfold in PA patients. Our data support the view that PA is not characterized by a specific capillaroscopic pattern and/or significant abnormalities of microvascular dynamics at the nailfold.