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Biomedical subjects

L A Christensen

Publications and source records attributed to L A Christensen.

34 records · Page 2Linked to original sources
PubMed1990

Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man.

The bioavailability of three pure 5-aminosalicylic (5-ASA) preparations (Asacol, Claversal, and Pentasa) was studied in 8 ileostomy patients and 12 normal subjects after 6 days of treatment with 2000 mg 5-ASA. The local bioavailability, reflected by the 5-ASA concentration was thereby measured at two clinically relevant areas of the gut: at the entrance to, and the exit from the colon. Estimates of the systemic bioavailability were obtained from the urinary excretions and the plasma values of 5-ASA and Acetyl-5-ASA (Ac-5-ASA) during the three regimens. The three preparations studied are designed to release 5-ASA at different levels in the intestine, but there was no significant difference in the 5-ASA concentrations in the ileostomy effluents (Asacol 1.8 mmol/L, Claversal 3.4 mmol/L, Pentasa 2.0 mmol/L, median values). However, we found a smaller urinary excretion of 5-ASA and Ac-5-ASA (5.2% vs Claversal 27.9% and Pentasa 23.0%, median values of ingested daily dose) and a lower concentration of Ac-5-ASA in the ileostomy effluents after Asacol treatment (0.8 mmol/L, median value) which indicates a more distal release from this preparation compared with Claversal (2.4 mmol/L, median value) and Pentasa (5.5 mmol/L, median value). In normal subjects a higher faecal water concentration of 5-ASA was found after Asacol (9.8 mmol/L, median value) compared with Claversal (5.0 mmol/L, median value), whereas no difference between the faecal water concentrations of Ac-5-ASA was found (Asacol 21.5 mmol/L, Claversal 21.6 mmol/L, median values). This can be explained by a larger systemic absorption of 5-ASA from Claversal, and accordingly Claversal treatment resulted in the largest urinary excretion of 5-ASA and Ac-5-ASA (43.7% vs Asacol 35.6% and Pentasa 31.6%, median values of ingested daily dose). The high Ac-5-ASA concentration in the ileostomy effluents and in the faeces after Pentasa, and the low plasma values, indicate a slow 5-ASA release from this preparation throughout the small and large intestine. The results of the study indicate that Asacol is released in the distal part of the small intestine, that Pentasa is gradually released in the small and large intestine, and that Claversal shows an intermediate release pattern.

Administration, Topical↗
PubMed1989

pH-profile and regional transit times of the normal gut measured by a radiotelemetry device.

The pH of the gut lumen was measured in 39 healthy persons using a pH-sensitive, radiotransmitting capsule. Thirteen persons were studied twice. The location of the capsule was determined by X-ray. The pH rose from 6.4 in the duodenum to 7.3 in the distal part of the small intestine. In 17 persons the pH dropped by 0.1-0.8 pH units during the last hours of the small intestinal transit. The pH was 5.7 in the caecum, but rose to 6.6 in the rectum. Gastric residence time was 1.1 h, small intestinal transit was 8 h, and colonic transit time was 17.5 h (median values). The results provide a firmer basis for prediction of the level, and the rate of release of active substance from pH-dependent sustained-release oral preparations.

Adolescent↗
PubMed1989

Effects of mesalazine substitution on salicylazosulfapyridine-induced seminal abnormalities in men with ulcerative colitis.

Some semen characteristics of eight male patients with clinically inactive ulcerative colitis were investigated. Semen analysis was carried out twice during salicylazosulfapyridine (SASP) treatment and repeated twice after at least 3 months' treatment with mesalazine. The motility variables all showed significant improvement during mesalazine treatment: the graded motility (p less than 0.05), motility in percentage (p less than 0.01), and the penetration in egg white (p less than 0.05). The semen plasma was analyzed for mesalazine and the metabolite Ac-mesalazine during both regimens. There was no difference in the semen plasma concentration of mesalazine during the two regimens, whereas Ac-mesalazine was significantly higher during mesalazine treatment than during SASP treatment, indicating that other SASP metabolites, most likely sulfapyridine, are the agent causing the abnormal sperm characteristics. We suggest that pure mesalazine preparations are a safer alternative in young men with chronic inflammatory bowel disease.

Adult↗
PubMed1989

5-Aminosalicylic acid derivatives. Clinical and pharmaceutical evaluation.

Several new 5-aminosalicylic acid (5-ASA) derivatives have been introduced for the treatment of chronic inflammatory bowel disease (CIBD). In azo-bond preparations, 5-ASA is linked to an inert carrier (Balsalazide) or to another 5-ASA molecule (Dipentum). The pharmacokinetic profile is similar to salazosulphapyridine (SASP) and the preparations are as effective as SASP in treatment of ulcerative colitis (UC) and with fewer side effects. In controlled release preparations (Asacol, Pentasa, Salofalk), 5-ASA is coated with compounds resistant to low pH, but which deliver 5-ASA to the intestines at various rates at higher pH values. The drugs are as effective as SASP in maintenance of remission and in the treatment of mild to moderate flare ups in UC. A larger systemic absorption is found for the three preparations compared to SASP. The controlled release preparations seem promising in the treatment of Crohn's disease, but further studies are needed. The controlled release preparations should be the drugs of choice in patients with UC allergic to or intolerant of SASP and to males who wish to have children.

Aminosalicylic Acids↗
PubMed1989

Hemocyte population changes during the immune response of Aedes aegypti to inoculated microfilariae of Dirofilaria immitis.

Ultrastructural and lectin-binding studies have established that the melanotic encapsulation reaction of Aedes aegypti Liverpool strain against inoculated Dirofilaria immitis microfilariae (mff) is a hemocyte-mediated reaction. Total hemocyte counts from mff-inoculated (= immune-activated), saline-inoculated, and uninoculated female A. aegypti were determined using a hemocoel perfusion technique. Total hemocyte populations in uninoculated mosquitoes were significantly larger in younger mosquitoes, but no significant change was noted as mosquitoes aged beyond 14 days. Hemocyte populations in immune-activated mosquitoes increased from 1 to 3 days postinoculation (PI) and decreased on days 4 and 5 PI. Hemocyte populations at 1 to 4 days PI were significantly elevated in mff-inoculated A. aegypti as compared with saline-inoculated controls. Saline-inoculated mosquitoes displayed little change in total hemocyte numbers from 1 to 5 days PI, and their hemocyte populations were similar to those seen in uninoculated insects of the same age. Experiments involving the inoculation of [3H]thymidine along with mff or saline alone and studies involving the administration of colchicine suggest that increased hemocyte populations in immune-activated A. aegypti are a result of mitotic division of circulating blood cells.

Aedes↗
PubMed1987

Perforated peptic ulcer--a complication in acute salicylate intoxication.

A patient with perforated peptic ulcer following acute salicylate intoxication is presented. The patient had reversible renal failure requiring dialysis therapy, but no abdominal symptoms were noticed until six days after arrival. At this time haematemesis and melaena were observed. Symptoms and objective findings were vague, but further investigations revealed a perforated prepyloric ulcer, which was successfully treated with cimetidine, The delay from intoxication to symptoms has previously been described and might be due to the analgetic properties of salicylates.

Acute Disease↗
PubMed1987

Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.

The influence of intestinal transit time on the release of 5-aminosalicylic acid (5-ASA) from a peroral, slow-release preparation (Pentasa) was studied at steady state in seven healthy volunteers. Daily dose was 1500 mg Pentasa, normal transit time (NTT) was 24 h (16-26 h) and accelerated transit time (ATT), caused by a laxative, was 5 h (4-9 h). Median total recovery (24 h, 5-ASA + acetyl-5-ASA) was 87% (61-129%) (NTT) and 81% (56-100%) (ATT), respectively, (P greater than 0.10). The total faecal excretion of 5-ASA (per cent of dose) increased from 16%, (9-21%) (NTT) to 29%, (16-38%) (ATT) (P less than 0.02). Free 5-ASA rose from 12% (4-19%) to 17% (10-25%), the retained part (in granules) from 4% (2-5%) to 12% (4-24%). Urinary excretion decreased correspondingly from 32% (19-59%) to 21% (11-38%), predominantly as Ac-5-ASA (P less than 0.05). Mean plasma Ac-5-ASA concentration decreased from 1.42 micrograms ml-1 to 0.86 microgram ml-1 (P less than 0.05). An almost complete release of 5-ASA from Pentasa takes place during NTT. At ATT conditions about 88% is released, indicating Pentasa to be an acceptable source of 5-ASA in diarrhoeal states.

Adult↗
PubMed1986

Abnormal duodenal loop in patients with irritable bowel syndrome.

The frequency of an abnormal duodenal loop (AD) was investigated in 36 patients with irritable bowel syndrome (IBS) and in a sex- and age-matched control group of patients with Crohn's disease. The frequency was significantly higher in the patients with IBS than in the control group (41% versus 18%; p less than 0.02). Among IBS patients with AD, the frequency of food-provoked pain was higher than in IBS patients with a normal duodenum (65% versus 21%; p less than 0.01). We conclude that AD may be one of the reasons for complaints in IBS.

Adult↗
PubMed1986

Microscopic appearance of the esophageal mucosa in a consecutive series of patients submitted to upper endoscopy. Correlation with gastroesophageal reflux symptoms and macroscopic findings.

The histologic finding of basal-layer hyperplasia and papillosis as consequences of gastroesophageal reflux still constitute an area of controversy. Consequently, a prospective study of symptoms and endoscopy and biopsy interpretation was undertaken in 200 patients consecutively submitted to upper endoscopy, whereof 12 were excluded. Complete agreement among all three variables was found in half of the patients and harmony between two of the variables in one fourth. In the last fourth the outcome was positive in one variable only, equally distributed among the symptoms, endoscopy, and histology. It is concluded that histology is of considerable value in gastroesophageal reflux disease.

Esophagoscopy↗
PubMed1986

Defense reactions of mosquitoes to filarial worms: effect of host age on the immune response to Dirofilaria immitis microfilariae.

The melanization response of Aedes aegypti black-eyed Liverpool strain (LVP) and Aedes trivittatus against intrathoracically inoculated Dirofilaria immitis microfilariae (mff) was assessed in mosquitoes less than 1, 14, 21, and 28 days after adult ecdysis. There was a significant decrease in the melanization response of A. aegypti 14 days of age and older at 1, 3, and 5 days postinoculation (PI) compared to less than 1-day-old mosquitoes. The response also was reduced significantly in 14- to 28-day-old A. trivittatus on days 1 and 3 PI. Although essentially 100% of recovered mff were melanized by day 5 PI in A. trivittatus, the amount of melanin deposited was much less than that seen in 0-day-old mosquitoes. Potential mechanisms responsible for a reduced immune competence in older mosquitoes and the possible relationship to vector potential are discussed.

Aedes↗
PubMed1983

Agar disk elution method for susceptibility testing of Mycobacterium marinum and Mycobacterium fortuitum complex to sulfonamides and antibiotics.

An agar disk elution method using round well plates, supplemented Mueller-Hinton agar, and commercial drug disks is described for susceptibility testing of Mycobacterium marinum and the rapidly growing mycobacteria to antibiotics and sulfonamides. By this method, 14 of 14 strains of M. marinum were susceptible to rifampin, doxycycline, minocycline, and trimethoprim-sulfamethoxazole. Identical results were obtained with Middlebrook 7H10 agar and drugs prepared from standard powders. With 58 isolates of Mycobacterium fortuitum and Mycobacterium chelonei, this method had a 92% correlation with broth minimal inhibitory concentration determinations for cefoxitin and greater than 98% for doxycycline, kanamycin, amikacin, and the sulfonamides. Sixty-nine percent of isolates of M. chelonei susceptible to amikacin on supplemented Mueller-Hinton agar were resistant on 7H10 agar, and 15 of 16 M. chelonei isolates susceptible to erythromycin in broth were resistant by disk elution when an endpoint of no growth was used with either agar. The agar disk elution method offers a practical method for testing of most antibacterial agents against these mycobacterial species.

Agar↗