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Biomedical subjects

B Eriksson

Publications and source records attributed to B Eriksson.

At least 235 records · Page 13Linked to original sources

Activity of the cytomegalovirus genome in the presence of PPi analogs.

PPi analogs and esters of these were studied for their effect on cytomegalovirus (CMV) multiplication. Five aromatic monoesters of phosphonoformate esterified either in the phosphono or the carboxylic group and two diesters were demonstrated to inhibit CMV DNA synthesis and late viral protein synthesis. In a direct assay, the monoesters but not the diesters inhibited CMV DNA polymerase activity. The production of early CMV antigens was not inhibited by any of the compounds. After incubation with either drug for periods up to 7 days, renewed viral production occurred on withdrawal of the compound. All inhibitory esters as well as PPi analogs showed a CMV multiplicity dependence. This was demonstrated both for CMV strain Ad.169 and for all tested CMV isolates. Evidence was found that the esters are hydrolyzed to phosphonoformate and, therefore, may be of importance as useful prodrugs in the specific therapy of CMV infections. The general phenomenon of reversibility to the productive state and the multiplicity dependence of CMV are important factors in any treatment schedule.

Antiviral Agents↗

Some new aspects on emesis gravidarum. Relations to clinical data, serum electrolytes, total protein and creatinine.

Although nausea and vomiting in early pregnancy is extremely common, very little information on the cause and course of this disorder is available in the literature. A prospective laboratory and clinical study of 102 consecutive healthy pregnant women was undertaken to evaluate nausea and vomiting in relation to clinical data, serum electrolytes, creatinine, total protein and hemoglobin. Multigravidae suffered from emesis gravidarum at a higher rate than did primigravidae. The frequency of emesis was especially high in women with short intergestational intervals. During pregnancy there was a decline in systolic blood pressure only in non-emetic women. The diastolic blood pressure in late pregnancy was significantly higher in emetic women than in non-emetic subjects. All laboratory values were within normal ranges. However, major changes occurred during pregnancy but some alterations were noted only in the emetic pregnancy. A different response to the hormonal situation is suggested to explain the dissimilarities between the emetic and non-emetic pregnancy.

Adult↗

Excision biopsy of the spleen by ultrasonic guidance.

Excision biopsy of the spleen was performed in 32 patients, using a recently invented instrument, which consists of a spring-trigger system for firing the two parts of a Tru-Cut needle. The biopsies were carried out under the guidance of an ultrasonic scanner. This technique yields sufficient material of high quality for a proper evaluation both of individual cells and the internal structure of the spleen. Eight patients had parenchymal abnormalities found by ultrasonic scanning: five had multiple abnormalities whereas three had a single abnormal area. Seven of these eight patients had a pathological spleen biopsy, consisting of Hodgkin's disease (four patients), "high-grade" malignant non-Hodgkin's lymphoma (two patients) or tuberculosis (one patient). In the other 24 patients with a normal ultrasonic picture of the splenic parenchyma five biopsies were pathological (3 cases of hairy-cell leukaemia, 1 of Gaucher's disease and 1 of Hodgkin's disease). Side-effects were: slight to moderate pain (16/32 patients) and bleeding requiring transfusion (4/32 patients). In one of these patients splenectomy was performed because of the bleeding. Two of the patients with bleeding complications suffered from hairy-cell leukaemia. It is concluded from this study that excision biopsy of the spleen is a diagnostic method which in some patients can replace splenectomy. The method seems to be valuable especially in patients with parenchymal abnormalities shown by ultrasonic scanning.

Adolescent↗

Marginal tissue reactions at osseointegrated titanium fixtures.

A longitudinal prospective and a cross-sectional retrospective study were undertaken in order to investigate the marginal tissue reactions at osseointegrated titanium fixtures and their abutments, supporting fixed bridges. Conventional clinical periodontal examination methods were combined with a serial-identical radiography. At the termination of the studies samples were taken for microbiological and histological analyses. Altogether the reactions at 220 fixtures in 40 jaws were explored. The clinical parameters were not found correlated with the other examination methods. Only 0.9 mm marginal bone was lost as a mean during the first year and then not more than 0.05-0.07 mm as a mean annually for the follow-up years. A stress-related remodelling of the perifixtural bone was observed radiographically. The microbiotia in the gingival pockets was dominated by cocci and non-motile rods (94%), indicating a favourable composition if similar findings had been observed at teeth. Half the number of the biopsies had no inflammatory infiltrates and a further third had the lowest inflammatory score in a 3-grade scale. The results indicate that the soft tissue surrounding the gingival part of osseointegrated fixtures remains remarkably healthy, which, in combination with the annual minor loss of marginal bone, is an indication of good long-term clinical prognosis.

Alveolar Process↗

Vestibulo-ocular disturbances in rats exposed to organic solvents.

The influence of different kinds of industrial solvents on the vestibular function of rats has been studied by recording nystagmus, induced by accelerated rotation. The effect was related to the blood levels of the solvents. One group of solvents, including halogenated saturated hydrocarbons like dichloromethane, caused depression of the vestibulo-oculomotor reflex (VOR). Another group, including benzene compounds like xylene, toluene, styrene and cumene and halogenated unsaturated hydrocarbons like trichloroethylene caused an excitation of the VOR. The most striking chemical similarity between the different solvents in the last group is the occurrence of double-bonds. If the animals were exposed simultaneously to solvents from both groups the excitatory effect prevailed and was even potentiated. It is suggested that solvents cause depression or excitation of the VOR by interaction with central pathways in the reticular formation and the cerebellum.

Animals↗

Early bladder training in patients with spina bifida.

A bladder training programme was applied in 43 children with myelomeningocele and complete urinary incontinence. In one group the training was commenced before the age of 3 years (mean age 1.3 years) and in another group between the ages of 3 and 13 years (mean age 5.8 years). The results as regards continence were better in the group with an early start of training, girls showing significantly better results than boys. Pharmacotherapy and cautious urethral surgery were valuable complements in selected cases. Vesico-ureteral reflux disappeared during treatment in 60% of the patients. Patients not showing significant improvement should be candidates for clean intermittent catheterization and/or cholinergic drugs, if detrusor hyperactivity is present.

Adolescent↗

Experimental septic shock: relative effects of treatment with antibiotics, crystalloid or colloid solution infusions and corticosteroids.

This study evaluates the relative effects of 2 combined antibiotics, a crystalloid solution, 4 3% colloid solutions, and a pharmacologic dose of corticosteroids, given alone and in combination for the treatment of Escherichia coli-induced septic shock. All treatments began 5.5 h after bacterial injection. Untreated septic rats had a mean survival time of 9.9 h. Antibiotics (trimethophrim and sulfamethoxazole) alone did not significantly increase mean survival time (11.0 h). No rats in either of these two groups survived 24 h. When antibiotics and dexamethasone were combined, 40% (4/10) rats lived longer than 24 h (p less than .05). With Ringer's solution infusion, the mean survival time was 8.7 h and 30% (3/10) lived longer than 24 h. When a 3% colloid solution was given, 50% (20/40) lived more than 24 h and 20% (8/40) lived more than 7 days. There was no significant difference between the 4 colloid solutions (albumin, dextran-40, dextran-70, hydroxyethyl starch). When Ringer's solution was combined with dexamethasone and antibiotics, 80% (8/10) lived more than 24 h and 20% (2/10) were long-term survivors. When the antibiotic drug was combined with a colloid solution and dexamethasone, all animals lived more than 24 h and 90% (9/10) lived more than 7 days. This study demonstrates the therapeutic value of an effective antibiotic drug for control of the infective organism, a colloid solution infusion to maintain blood volume and circulation, and corticosteroids for still largely unknown reasons.

Animals↗

Synthesis and antiviral activity of distamycin A analogues: substitutions on the different pyrrole nitrogens and in the amidine function.

Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.

Animals↗

Capillary filtration in the small intestine after irradiation. An experimental study in the cat.

Capillary filtration in the experimentally irradiated small intestine of the cat was studied by measuring the capillary filtration coefficient (CFC). Segments of the small intestine were exposed to X rays of 15, 20, or 25 Gy and studied during the acute gastrointestinal radiation syndrome (4th day) and later (1 and 4 months). On the 4th day CFC had decreased to less than 60% of the original value. Increasing doses resulted in decreasing CFC. One month after irradiation CFC increased, but not to normal levels. After 4 months no further improvement was observed. With the higher doses a secondary decrease in CFC appeared, which might indicate a late effect of irradiation on capillary function.

Animals↗

Ultrastructural aspects of capillary function in irradiated bowel. An experimental study in the cat.

Irradiated small intestine of the cat has decreased capillary function measured as capillary filtration. This decrease may be due to changes in capillary permeability or decreased capillary area. An electron microscopic study was carried out to examine whether there were any ultrastructural changes consistent with impaired permeability. Cat ileum was irradiated with doses from 10 to 25 Gy and examined 4 days, 1 month, and 4 months after irradiation. In the acute phase (4 days) degenerative endothelial changes were seen and increased with dose. Congestion and microthrombi were also observed. One month after irradiation endothelial changes were still seen after 20 and 25 Gy, and an aggregation of fibrous matter adjacent to the capillary wall was prominent. The endothelial changes were subtle after 4 months, but the pericapillary and stromal fibrosis increased, and an increasing number of collagen fibrils appeared. Micropores disappeared after 20 and 25 Gy but returned later. Pinocytic vesicles were observed after all doses and intervals. The initial decrease in capillary filtration coefficient after irradiation may partly be due to permeability changes caused by endothelial degeneration, whereas the late decrease parallels the increasing pericapillary fibrosis.

Animals↗

Ectopic intestinal glands after segmental small bowel irradiation in the cat.

Following segmental irradiation of the small bowel, 5 of 64 cats demonstrated ectopic intestinal glands in the submucosal tissue. In addition, one of these 5 cats had foci of abnormal glands in the muscularis mucosae. In 2 of the 5 animals, cellular polymorphism, nucleolar irregularity and loss of cellular polarity were present in irradiation-induced ectopic intestinal glands. The review of the literature indicates that intestinal irradiation may induce intestinal adenocarcinomas with metastatic growth. The possibility that ectopic intestinal glands are precancerous lesions in the irradiated cat is discussed.

Animals↗

Pyrophosphate analogues as inhibitors of DNA polymerases of cytomegalovirus, herpes simplex virus and cellular origin.

Several pyrophosphate analogues have been compared for their ability to inhibit the activities of isolated cytomegalovirus (CMV) DNA polymerase, herpes simplex virus type 1 (HSV 1) DNA polymerase and calf thymus DNA polymerase alpha. The most effective inhibitors were phosphonoformate and phosphonoacetate. Although not identical, the structural requirements for compounds inhibitory to CMV and HSV-1 DNA polymerase were specific, with two negatively charged groups in close vicinity. The CMV DNA polymerase was more susceptible to certain phosphonoacetates containing bulky hydrophobic alpha-substituents than was the HSV-1 DNA polymerase. No example of the converse preference was found. The inhibition of CMV DNA polymerase by phosphonoformate, hypophosphate, alpha-hydroxyphosphonoacetate and alpha-nonylphosphonoacetate was linear non-competitive with the deoxyribonucleoside triphosphates as variable substrates. Phosphonoformate, phosphonoacetate, and to a lesser extent alpha-hydroxyphosphonoacetate, carbonyldiphosphonate and alpha-nonylphosphonoacetate also inhibited the focus formation by CMV in cell-culture.

Animals↗

Inhibition of reverse transcriptase activity of avian myeloblastosis virus by pyrophosphate analogues.

Several pyrophosphate analogues have been studied for their effects on avian myeloblastosis virus reverse transcriptase and on cellular DNA polymerase alpha. Examination of structure-activity relationships for these compounds revealed that two acidic groups connected by a short bridge were necessary, but not sufficient, for inhibition of the enzyme activities. Foscarnet sodium (trisodium phosphonoformate) was the most potent inhibitor of reverse transcriptase, giving non-competitive inhibition of reactions primed by (rA)n . (dT)12-18, (rC)n . (dG)12-18, (dC)n . (dG)12-18, and activated DNA. Carbonyldiphosphonate and 2-hydroxyphosphonoacetate also caused non-competitive inhibition patterns, whereas hypophosphate and imidodiphosphonate inhibited AMV reverse transcriptase in a competitive, non-linear manner. The reverse transcriptase reactions directed by (rA)n . (dT)12-18 and activated DNA were most affected by the non-competitive inhibitors. Hypophosphate and imidodiphosphonate inhibited preferentially reactions primed by (dC)n . (dG)12-18 and activated DNA. In all cases the (rC)n . (dG)12-18 directed reaction was the least affected.

Avian Leukosis Virus↗