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Biomedical subjects

L Hendel

Publications and source records attributed to L Hendel.

At least 19 recordsLinked to original sources
PubMed2001

Oesophageal pressure-cross-sectional area distributions and secondary peristalsis in relation to subclassification of systemic sclerosis.

The aim of the present study was to correlate the severity of oesophageal motor dysfunction with the severity of cutaneous disease in systemic sclerosis (SS). Patients were divided into three groups based on the degree of skin involvement: type I, acrosclerosis distal to the wrist; type II, scleroderma extending above the wrist in proximal direction; type III, diffuse cutaneous systemic sclerosis. Impedance planimetry employing distensions with pressures up to 5 kPa with the concomitant measurement of oesophageal cross-sectional area (CSA) was used in combination with standard oesophageal manometry. Measurements were made at 7 and 15 cm above the lower oesophageal sphincter (LOS). Thirty patients (16 type I, six type II and eight type III patients) and 23 normal controls were included. LOS pressure was lower in SS patients than in normal patients, with the lowest values in type III. The CSAs were higher in SS patients than in controls at both sites (P < 0.001). The CSAs at the distal site were highest in type III, as compared to type I and II (P < 0.03). The CSA at the highest induced pressure (5.0 kPa) was 613 +/- 45, 719 +/- 79, and 808 +/- 115 mm2 in types I, II and III, respectively. No differences in CSA were found at the proximal site between the three types of SS. The distensibility did not differ between SS and normal patients at the distal site. The distensibility was lowest in SS patients (P < 0.001) at the proximal distension site. The distensibility did not vary with the type of SS at either site. Significant differences in contraction frequency of the secondary peristalsis as function of wall tension were demonstrated between the SS patients and controls at the distal site (P < 0.05). No differences were found at the proximal site. The contraction frequency and amplitude at the distal and proximal sites did not differ among the three types. In conclusion for most parameters studied, SS patients differed from normal patients. Among SS types, the most pronounced changes were found in type III.

Adult↗
PubMed1997

Impedance planimetric characterization of esophagus in systemic sclerosis patients with severe involvement of esophagus.

This study was designed to evaluate the distensibility and secondary peristalsis of the esophagus in patients suffering from systemic sclerosis with severe esophageal involvement. Balloon distension with impedance planimetric measurement of luminal cross-sectional area was done 7 and 15 cm above the lower esophageal sphincter in 13 patients and nine healthy controls. The controls were studied both with and without receiving the anticholinergic drug butylscopolamine. The cross-sectional area--pressure relations were nonlinear with the largest cross-sectional area in patients at both measuring sites when compared to controls (P < 0.001). The anticholinergic drug butylscopolamine increased the cross-sectional area in controls (P < 0.001). The cross-sectional area distensibility, defined as CSA0(-1) delta CSA delta P-1 did not differ between patients and controls. Balloon distensions elicited contractions proximal to the distension site. The amplitude and frequency of contractions at the distal distension site were significantly reduced in the patients when compared to the controls (P < 0.05). In conclusion, the distal esophagus is most severely affected in patients with systemic sclerosis with increased cross-sectional area and impaired peristalsis.

Adult↗
PubMed1996

Monitoring of omeprazole treatment in gastro-oesophageal reflux disease.

OBJECTIVE: To test our standard dosing regimen in omeprazole treatment of gastro-oesophageal reflux disease (GORD) and to determine whether 'non-responders' could be pinpointed. DESIGN: A reverse dose-response examination using increasing doses of omeprazole. The study was conducted as an open consecutive clinical study. Response was measured by 24-h pH-metry, symptoms, endoscopy and histopathology. SETTING: All patients had been referred to one of the partaking departments for evaluation of oesophageal reflux symptoms. PATIENTS: A total of 62 patients were included, 29 with systemic sclerosis and 33 consecutively included patients suffering from idiopathic oesophageal reflux. RESULTS: Approximately one-third of the patients required doses higher than 40 mg of omeprazole/day (up to 140 mg/day) to abolish GOR. No cases of tachyphylaxia or bile-induced oesophagitis were seen in this study. In all patients subjected to dose titration we were able to achieve healing of oesophagitis assessed by symptom scoring, endoscopy and histopathology. No prediction of final dose of omeprazole could be made. CONCLUSION: Four weeks after reaching a dose level of omeprazole that ensured the abolition of GOR, healing of oesophagitis according to endoscopic/histological evaluation was obtained in all patients. Persistent oesophagitis, i.e. bile induced, was not found.

Adult↗
PubMed1995

Morning or evening dosage of omeprazole for gastro-oesophageal reflux disease?

BACKGROUND AND AIMS: When routinely checking patients receiving omeprazole treatment for gastro-oesophageal reflux, we have been finding patients with surprisingly low nocturnal gastric pH. The aim of this study was to evaluate the impact of timing of the 40 mg omeprazole once daily regimen. METHODS: We evaluated the difference in effect of 40 mg omeprazole, given as a morning or evening dose, in 17 patients with gastro-oesophageal reflux disease. Gastric and oesophageal pH was recorded by portable 24-h two-channel pH-metry in a cross-over design of 14 days of morning and 14 days of evening administration. RESULTS: In five patients pathological reflux was abolished by both regimens, four only during morning dosage, and three only during evening dosage. In the remaining five patients abolition of pathological reflux was not achieved. The therapeutic outcome and patient preference for morning or evening administration were closely related to the individual oesophageal pH curves. Patients with reflux induced by physical activity had a clear preference for morning dosage, patients with nocturnal reflux showed a clear preference for evening dosage. Gastric pH profiles showed a high inter-individual variation; paired statistics, however, revealed a significant impact of dosage timing on the gastric pH profile. After morning dosage the work-day part (the first 7 h) of the gastric pH profile is 0.72 +/- 0.91 (mean difference of pairs +/- s.d.) higher than after evening dosage (P < 0.01). After evening dosage the gastric pH during the supine period is 0.64 +/- 0.83 (mean difference of pairs +/- s.d.) higher than after morning dosage (P = 0.02). CONCLUSION: The timing of a 40 mg omeprazole dosage regimen has a clinically significant impact on the 24-h pH profile, and that--by relating to the patient 24-hour oesophageal pH-metry in combination with the patient symptomatology--the timing of this dosage is highly important for therapeutic efficacy.

Adult↗
PubMed1994

Esophageal and small intestinal manifestations of progressive systemic sclerosis. A clinical and experimental study.

Progressive systemic sclerosis (PSS) is a systemic disease with a high frequency of gastro-intestinal involvement. The present thesis deals with the occurrence of, the complications to, and the treatment of the esophageal manifestations combined with more experimental studies on small intestine manifestations. The conclusions in this thesis are based on results achieved in 9 original previously published papers. The pattern of esophageal dysmotility is thoroughly evaluated in 156 consecutive PSS patients and is found to be identical to what is found in other large series of PSS patients. In paper no. I dysmotility variables are correlated to the occurrence of gastroesophageal reflux (GER) and it is shown that also in this group of patients with well defined dysmotility problems the only reliable GER test is pH-metry. Esophageal dysmotility furthers esophageal candidosis, which is further facilitated by anti-reflux treatment. This problem is evaluated in paper no. V. Progression of esophageal dysmotility in spite of D-penicillamine treatment is shown in paper no. VII and confirms the non-stable condition of the PSS patient in regard to esophageal manifestations and complications. This point is also outlined in paper no. IX concerning surveillance and continuous treatment of esophageal PSS. Esophageal stricturing is a well-known entity in PSS. The etiologic question of esophageal stricturing being a manifestation of PSS and/or a peptic complication, is approached in paper no. VIII. PSS manifestations of the small intestine are not as frequent as in the esophagus, in the present material only 19% presented with X-ray changes. However, bacterial count of duodenal juice as an indirect measurement of small intestinal dysmotility in paper no. VI indicates a much larger percentage of small intestinal involvement than revealed by X-ray. In paper no. VI the exocrine pancreatic function was assessed in 16 PSS patients. It is shown that the endogenous stimulation capacity is preserved even in spite of demonstrable small intestinal PSS involvement and that exocrine pancreatic function is frequently reduced, but rarely to a degree of clinical significance. Small intestinal enterocyte function is evaluated according to the ability to hydrolyse folatepolyglutamates and to absorb D-penicillamine, and is in both respects found less than normal. In an ultrastructural evaluation (paper II) the enterocytes presented signs of defective fat transport. PSS manifestations of the gastrointestinal tract are frequent and burdensome to the patient. Omeprazole and new prokinetic drugs have rendered new therapeutic potentialities, which, however, more than ever demand constant surveillance and individualized regulation of treatment.

Clinical Trials as Topic↗
PubMed1992

Gastrointestinal transit times of radiolabeled meal in progressive systemic sclerosis.

Gastrointestinal transit times were measured in 12 patients with progressive systemic sclerosis. The CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) was found in all patients. None of the patients reported complaints referable to specific gastric, small intestinal, or colonic involvement. The patient group had an increased mean gastric emptying time of 99mTc-labeled cellulose fiber when compared with 16 healthy controls [1.17 (0.89-1.38) hr [median (range)] vs 0.84 (0.56-1.88) hr; P less than 0.02], whereas mean gastric emptying time of 2- to 3-mm 111In-labeled plastic particles was unaffected [1.86 (0.99-2.74) hr vs 1.50 (0.92-2.51) hr; NS]. No difference was observed in mean small intestinal transit time of cellulose fiber [4.33 (0.50-7.04) hr vs 3.74 (2.09-7.59) hr; NS] or plastic particles [4.21 (2.00-6.25) hr vs 3.53 (1.50-6.70) hr; NS] between patients and controls. The patient group had an increased mean colonic transit time of plastic particles [47 (24-116) hr vs 29 (18-46) hr; P less than 0.01]. These findings suggest that asymptomatic delay in gastric emptying and colonic transit is frequent in patients with progressive systemic sclerosis.

Adult↗
PubMed1992

Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis.

Twenty-five patients with systemic sclerosis and severe gastro-oesophageal reflux disease were treated with 20-80 mg omeprazole daily for up to 5 years. Efficacy of treatment was assessed by symptom score, by endoscopic and histopathological surveillance of the oesophageal and gastric mucosa, and by laboratory screening including serum gastrin concentration. Statistically significant relief of symptoms and healing of oesophagitis confirmed the efficacy of this treatment. However, complete healing of oesophagitis was not achieved in half of the patients due to residual gastro-oesophageal acid reflux. Repeated adjustments of the maintenance dose of omeprazole may be needed for this group of patients. From the safety point-of-view, nothing was observed to discourage the long-term use of omeprazole in this group of patients.

Adult↗
PubMed1991

Hydroxyproline in the oesophageal mucosa of patients with progressive systemic sclerosis during omeprazole-induced healing of reflux oesophagitis.

Hydroxyproline concentration in oesophageal mucosal biopsies was used as an index of collagen in an attempt to evaluate the potential for stricture formation in patients with progressive systemic sclerosis. Eight patients suffering from progressive systemic sclerosis with complicating gastro-oesophageal reflux, 8 patients with idiopathic gastro-oesophageal reflux, and 7 normal controls were compared. Acid gastro-oesophageal reflux was assessed with 24-h pH-metry; degree of oesophagitis was evaluated both endoscopically and histopathologically. The patients with progressive systemic sclerosis were investigated at the start of the study and later when healing of oesophagitis was accomplished with omeprazole therapy. The hydroxyproline concentration was significantly increased (P less than 0.01) in the oesophageal mucosa from patients with progressive systemic sclerosis (median 21.8 nmol/mg) as compared to patients with idiopathic gastro-oesophageal reflux (median 6.4 nmol/mg) and normal controls (median 8.1 nmol/mg). Hydroxyproline concentration in oesophageal mucosa from patients with progressive systemic sclerosis decreased significantly and to a normal level (median 6.5 nmol/pg; P = 0.014) when healing of oesophagitis was achieved.

Adult↗
PubMed1989

Exocrine pancreatic function in patients with progressive systemic sclerosis.

The exocrine pancreatic function was investigated in 16 patients with progressive systemic sclerosis by means of a meal test (Lundh test) and in 9 of the patients by the secretin-cholecystokinin test as well. Gastrointestinal involvement with progressive systemic sclerosis was evaluated by esophageal manometry and by routine roentgenographic series of the small bowel. Fecal fat excretion measurement, the D-xylose absorption test, and a small-intestinal biopsy procedure were carried out. Duodenal juice was cultured and bacterial counts were estimated. One-third of the patients had reduced exocrine pancreatic function, but only four patients had unequivocally a reduction that could be of clinical importance. The results obtained with the meal test were in accordance with the secretin-cholecystokinin test, indicating a preserved capacity for endogenous stimulation.

Adult↗
PubMed1989

The progress of oesophageal involvement in progressive systemic sclerosis during D-penicillamine treatment.

In 21 patients with initial signs of progressive systemic sclerosis, oesophageal motility was monitored manometrically from the start of D-penicillamine treatment and over a period of up to 5 years. Urinary excretion of the collagen-specific amino acids hydroxyproline and hydroxylysine, and of proline was used as a guideline for monitoring the bioavailability of D-penicillamine. D-penicillamine therapy was found to be unable to arrest the progress of oesophageal involvement. A downward trend over time--statistically significant at p = 0.03, p = 0.02, and p less than 0.005--was found for lower oesophageal sphincter pressure, peristaltic wave pressure in the distal third, and peristaltic wave pressure in the middle third of the oesophagus, respectively.

Esophagitis↗
PubMed1988

Esophageal candidosis in progressive systemic sclerosis: occurrence, significance, and treatment with fluconazole.

Esophageal mucosal brushings from 51 consecutive patients with progressive systemic sclerosis (PSS) (group I), 18 PSS patients continuously treated with high-dose ranitidine or omeprazole (group II), 34 controls referred to the outpatient clinic for endoscopy (group III), and 10 patients receiving long-term potent antireflux therapy for idiopathic gastroesophageal reflux (group IV) were cultured for Candida albicans. There were 44%, 89%, 9%, and 0% Candida albicans culture-positive patients in groups I through IV, respectively. Fifteen patients with candida esophagitis from group II were treated with fluconazole systemically. Eleven and 14 patients became culture-negative after 2 and 4 weeks' treatment, respectively. Three months after fluconazole withdrawal the recurrence rate was 100%. It is concluded that esophageal dysmotility predisposes for candidosis. Adding gastric acid inhibitory treatment to dysmotility enhances the risk significantly (p less than 0.01). The efficiency of fluconazole treatment was close to 100%, but so was the recurrence rate within a short period.

Adult↗
PubMed1987

Ultrastructure of the small intestinal mucosa in progressive systemic sclerosis (PSS).

The present study deals with ultrastructural changes of jejunal absorptive epithelium in mucosal biopsy specimens from eleven patients with progressive systemic sclerosis (PSS). Epithelial cells showed cytoplasmic condensations with cholesterol clefts and fat droplets. Intercellular spaces of the epithelium were dilated with deposits of fat droplets, while tight junctions and villi preserved their normal structures. Goblet cells and entero-endocrine cells showed no changes. In the lamina propria, fat droplets were observed as well. Vessels were strongly dilated and in 2 patients contained conglomerates of thrombocytes. Perivascular cell infiltrates consisted of lymphocytes, macrophages and mast cells, while plasma cells were scarcely seen; in 2 patients, plasma cells were abundant. Collagen fibrils, elastic fibres, and nerves showed no definite changes. The findings of epithelial cell degeneration and fat droplet deposits indicate dysfunction of jejunal absorptive epithelial cells in PSS.

Adult↗
PubMed1987

Enterocyte function in progressive systemic sclerosis as estimated by the deconjugation of pteroyltriglutamate to folic acid.

As a measure of enterocyte function, the deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid to folic acid and subsequent active absorption was measured in 19 patients with progressive systemic sclerosis and compared with 14 controls. The absorption step of folic acid was identical in the two groups, while deconjugation of pteroyl-L-glutamyl-gamma-L-glutamyl-gamma-L-glutamic acid was significantly decreased in the patients with progressive systemic sclerosis. This observation suggests a primary epithelial defect of the small intestine in patients with progressive systemic sclerosis.

Adult↗
PubMed1987

Esophageal manometry and pH-probe monitoring in the evaluation of gastroesophageal reflux in patients with progressive systemic sclerosis.

Fifty-five patients with progressive systemic sclerosis (PSS) were evaluated with esophageal manometry, 12-h pH-probe monitoring in esophagus, and registration of symptoms of gastroesophageal reflux (GER). Thirty-nine patients had symptoms suggestive of GER. The 12-h pH-monitoring showed pathologic GER in 30 patients. We found that 33% of the patients with symptoms did not have pathologic GER, and 25% of the patients without symptoms had pathologic GER. Characteristic changes of impaired motility in the esophagus were found in 46 patients. When combining esophageal manometry, reflux measurement, and symptoms of GER, we found a positive correlation in 60% of patients with reduced peristalsis in the lower two-thirds of the esophagus and GER. We therefore recommend sensitive esophageal pH-monitoring in all PSS patients to ensure treatment of patients with pathologic GER.

Adult↗
PubMed1987

Bioavailability of D-penicillamine in relation to gastrointestinal involvement of generalized scleroderma.

The bioavailability of D-penicillamine was measured in 24 patients with generalized scleroderma (Progressive Systemic Sclerosis, PSS). Esophageal changes characteristic of generalized scleroderma were present in 15 of the patients, and 3 of those patients had duodenal involvements as well. The plasma concentrations of D-penicillamine were measured at 0 h, 1 h, 2 h, and 4 h after an oral dose of 300 mg D-penicillamine. Patients with duodenal and/or esophageal changes specific for scleroderma had significantly lower bioavailability of D-penicillamine than scleroderma patients without gastrointestinal manifestations. The decreased plasma D-penicillamine in scleroderma patients with involvement of the gastrointestinal tract may be due to an increased degradation of D-penicillamine in the gastrointestinal tract and/or an impaired absorption of the drug. Since the plasma level of D-penicillamine is so sensitive to pathological changes of the gastrointestinal tract, it may be advisable to adjust the dose of D-penicillamine on the basis of measurements of the plasma concentration of D-penicillamine.

Administration, Oral↗
PubMed1986

Enterocyte-labelling index in the duodenal mucosa of patients with progressive systemic sclerosis (PSS).

Ten patients with progressive systemic sclerosis (PSS), 4 patients with other gastro-intestinal diseases and 5 normal controls, underwent small intestinal biopsy procedure. The biopsy material was incubated with tritiated thymidine and processed for auto-radiography. The labelling index (LI) in the small intestinal mucosa was estimated. The LI in PSS patients with duodenal involvement was significantly higher than the LI in PSS patients without duodenal involvement. In the latter group, the LI was at the same level as in normal controls. The LI in patients with other gastro-intestinal diseases, with diarrhoea as a main symptom, was not significantly different from the LI found in duodenal PSS.

Adult↗