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Biomedical subjects

H Hildebrand

Publications and source records attributed to H Hildebrand.

At least 37 records · Page 2Linked to original sources

Growth as a parameter of inflammation in Crohn's disease, using roentgen stereophotogrammetric analysis.

Growth rate was measured in 12 children with Crohn's disease and growth retardation, using roentgen stereophotogrammetric analysis. The method was chosen as it provides an opportunity to record growth rate accurately during short periods of time. Growth was followed at variable intervals of 4-12 weeks depending on the clinical situation. Growth rate was shown to correlate with symptoms, laboratory tests and nitrogen balance. These findings indicate that growth, when it is affected, fluctuates in a similar way as albumin, acute phase proteins and symptoms, all assumed to reflect the disease activity. Short-term growth measurements appear to be helpful in monitoring the disease progress or response to therapy in children with Crohn's disease, particularly when growth retardation is the only manifestation of the disease.

Adolescent↗

Incidence and prevalence of inflammatory bowel disease in children in south-western Sweden.

The incidence and prevalence of inflammatory bowel disease were estimated in all children less than 16 years of age living in the city of Göteborg and in three countries in South-Western Sweden, from 1983 to 1987. One hundred and thirty-two patients were classified according to set criteria into one of four diagnostic categories: ulcerative colitis, Crohn's disease, probable Crohn's disease and indeterminate colitis. The crude incidence of inflammatory bowel disease was 5.3 per 100,000 children per year and the prevalence 21.5 per 100,000 children. This study lends support to the hypothesis that Crohn's disease has increased among Swedish children. Crohn's disease now appears to be at least as common as ulcerative colitis. Thirty-five of 55 patients first classified as indeterminate colitis or probable Crohn's disease later fulfilled the criteria of ulcerative colitis or Crohn's disease during a mean follow-up period of 4.6 years. This study emphasizes the importance, in epidemiological studies of inflammatory bowel disease, of including those cases where a definite diagnosis of ulcerative colitis or Crohn's disease cannot be established initially and of re-evaluating the initial diagnosis regularly.

Adolescent↗

[Possibilities for preoperative determination of transplant quality using an osteoporosis index].

Preprosthetic procedures and reconstructive measurements are typically performed in elder patients. In this age group osteoporotic changes of the skeleton are common. The facial bones are persistently envolved within this process. Preoperative assessment of bone height and width are nowadays routine procedures in preprosthetic surgery, little attention is paid towards the bone quality at the recipient site of dental implants and the donor and recipient sites of bone-grafts. This study is performed to investigate the possibility to evaluate the bone quality prior to preprosthetic and reconstructive operations. The amount of the mineralization of the skeleton was determined in 17 patients which were scheduled for preprosthetic and reconstructive surgery with the help of Dual Energy X-Ray Absorptiometry (DEXA). The amount of mineralization of the skeleton and the osteoporosis-index, which were determined with the help of DPX-scans, are representative also for the facial skeleton. In our preliminary study patients with a low skeletal mineralization have a tendency towards increased complications after preprosthetic and bone-graft surgery. In addition the preoperative assessment of bone quality serves the basis for a accompanying osteoporosis therapy.

Adult↗

Chondrotoxicity of quinolones in vivo and in vitro.

Chondrotoxicity is a rare toxicological finding which is observed in dogs after administration of quinolone antibacterials. To study this effect chondrocytes from articular cartilage of dogs were isolated, and incubated with quinolone derivatives. The effects on cell viability, mitochondrial dehydrogenase, and proteoglycan synthesis were determined. These results were compared with in vivo findings in dogs treated with these quinolones. It was concluded that inhibition of mitochondrial dehydrogenase activity and of proteoglycan synthesis are major reasons for cartilage damage. Therefore this in vitro model is capable of identifying strongly arthropathogenic quinolones without the need of performing animal studies.

Animals↗

Crossover trials, degrees of freedom, the carryover problem and its dual.

The problem of carryover in crossover trials has received a great deal of attention in the statistical literature. Carryover is just one form of period by treatment interaction; yet a parallel problem of patient by treatment interaction, which may be regarded as dual to that of carryover, has received little attention. We suggest that the phenomenon of patient by treatment interaction requires a repeated measures approach to the analysis of crossover trials. A simple solution using predefined contrasts is presented and illustrated by example.

Analysis of Variance↗

Characterization of oral sustained release preparations of iloprost in a pig model by plasma level monitoring.

Iloprost (5-[(E)-1S,5S,6R,7R)-7-hydroxy-6-[(E)-3S,4RS)-3-hydroxy-4- methyl-octen-6-inyl]-bicyclo[3.3.0]-oct-3-ylidene)-pentanoic acid) is a chemically stable PGI2-mimetic with high pharmacological potency. Therapeutic efficacy in various disease stages (e.g. peripheral arterial occlusive disease, M. Raynaud and thromboangiitis obliterans) was shown after repeated once-a-day infusion treatment over several weeks. In order to facilitate drug therapy an oral dosage form is desirable. As a first step, a suitable animal model was needed to screen several formulation variants prior to characterization of promising candidates in man. After intravenous infusion treatment, the pig exhibited - similar to man - strictly dose-dependent steady state plasma levels and a total iloprost clearance of approximately 26 ml/min/kg (man approximately 20 ml/min/kg). Partial similarity of physiology and anatomy of the GI-tract and the possibility to administer intact capsule dosage forms led to a series of screen experiments with several sustained release preparations (pellets and matrix tablets) of iloprost exhibiting different in-vitro drug release profiles. A good correlation of in-vitro dissolution and in vivo plasma level data was obtained for all preparations containing the pellet neutral polymer. For the other formulations slight differences between duration of liberation and plasma level or time of maximum dissolution rate and tmax of plasma levels was observed. In the case of ionized polymers or matrix tablets, in vitro dissolution profiles were slightly different from in vivo data. This might be due to different dissolution behaviour in the gastro-intestinal tract. The pig seems to be a model that is suitable for verifying drug liberation profile in-vivo. Based upon plasma levels obtained in animals, selection of a formulation for characterization in man can be made.

Administration, Oral↗

Chronic inflammatory bowel disease in children and adolescents in Sweden.

The incidence and prevalence of chronic inflammatory bowel disease (IBD) in children was established during 1984 and 1985 in a prospective study in Sweden. The patients with IBD were classified as having ulcerative colitis (UC), Crohn's disease (CD), probable Crohn's disease (PCD), and indeterminate colitis (IC) according to defined histopathologic, endoscopic, and radiologic criteria. The study covered 1.51 million children less than 16 years of age (93% of all children in Sweden). The incidence of IBD was 5.0 and 4.5 and the prevalence was 17.6 and 18.2 per 100,000 children during the 2 years, respectively. The mean prevalence of UC was 7.5 per 100,000 and of CD + PCD was 6.2 per 100,000. The prevalence of IC was 4.2 per 100,000, which corresponds to 23% of the children with IBD.

Adolescent↗

Roentgen stereophotogrammetric short-term analysis of growth rate in children operated for Crohn's disease.

Roentgen stereophotogrammetry is a new method for short term analysis of growth rate. Growth is measured over the growth zone in the distal fibula and is a fraction of the total statural growth. Normal growth rate in the distal fibula is about 15 micrograms/day at a total growth rate of 5 cm/year. The method was used to follow growth six months before and six months after surgery in six growth retarded children with Crohn's disease. Growth rate increased significantly (p less than 0.01) within three months after surgery from 5.8 microns/day before operation to 15.8 microns/day three months after operation and six months postoperatively had reached 18.0 micron/day. Improved growth could be recorded as early as four weeks after operation. The Roentgen stereophotogrammetric analysis (RSA) gives a unique possibility to follow short-term changes in growth rate in children with disturbed growth and to use growth rate as a quick assessment of response.

Adolescent↗

Isolated co-lipase deficiency in two brothers.

Two normally developed Assyrian brothers with isolated pancreatic co-lipase deficiency are described. They presented at the age of 5-6 years with loose stools. They had steatorrhoea, and analysis of exocrine pancreatic enzymes in the small intestine showed co-lipase deficiency, while amylase, chymotrypsin, trypsin and lipase were normal. Intraduodenal infusion of purified co-lipase improved fat digestion measured by the triolein breath test. Their steatorrhoea diminished on treatment with enteric-coated pancreatic enzymes.

Bile Acids and Salts↗

Lipase and co-lipase activities of human small intestinal contents after a liquid test meal.

Methods for the determination of pancreatic lipase in small intestinal content have been re-evaluated in the light of the presence of co-lipase therein. A method is described for the determination of co-lipase in intestinal content based on its property to reactivate bile-salt-inhibited lipase. Figures are given for lipase and co-lipase activities in intestinal contents of normal humans aged 1-22. These two components originating in the pancreatic juice vary in a parallel fashion, and no variations with age were apparent. A simple diagnostic criterion is given to detect a possible specific co-lipase deficiency.

Adolescent↗

Urinary antigens as markers of papillary toxicity. II: Application of monoclonal antibodies for the determination of papillary antigens in rat urine.

We have previously reported the preparation of monoclonal antibodies specific for antigens localized in the rat renal papilla. Three of the monoclonal antibodies reacting with antigens localized in papillary and cortical collecting duct epithelia were selected for the development of enzyme-linked immunosorbent assay (ELISA)-type assays. The papillary antigens ('PapA') determined in these tests were designated PapAl (applying the monoclonal antibody PapX 5C10), PapA2 (applying the monoclonal antibody PapX 12F6), and PapA3 (applying the monoclonal antibody PapXI 3C7). Using these assays antigen excretion was determined in the urine of rats. Depending on the test compound used. the application route, and the dose, the observed antigen release patterns differed. Whereas after a single intraperitoneal application of 2-bromoethanamine or of propyleneimine an increased release of PapA1 but not of the two other antigens was observed oral application of bromoethanamine had minor effects. In contrast, both a single intraperitoneal application or repeated oral applications of indomethacin resulted in an increased release of all the three antigens. Daily application of ipsapirone in the diet or in drinking water resulted in significantly elevated urinary release of PapAl which increased incrementally for the duration of the application. Release of PapA2 and PapA3 was not affected and remained in the normal range. These results show that with the tests developed changes in the rat renal papilla caused by xenobiotics can be detected early by urinary analysis and monitored during follow-up studies. Moreover. the different antigen release patterns obtained after application of the different compounds suggest a possible differing mode of action.

Animals↗