Prevalence of upper gastrointestinal mucosal abnormalities at a rheumatology clinic.
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Biomedical subjects
Publications and source records attributed to J Senior.
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1 The effect of a single subcutaneous dose of tamoxifen on the rat uterotrophic response was investigated. 2 The parameters examined were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors. 3 Tamoxifen or its metabolites proved to be capable of eliciting a uterotrophic response of 35-42 days duration. The changes seen in uterine blood flow and weight are discussed in relation to oestrogen receptor distribution.
Incubation of small unilamellar liposomes composed of equimolar phospholipid and cholesterol with mouse IgG or mouse monoclonal IgG1 for up to 24 h resulted in considerable (34-89%) adsorption of the protein onto the liposomal surface. Immunoglobulin remained adsorbed after exposure to mouse plasma and, in the case of monoclonal (anti-HBSAg) IgG1, was able to mediate association of the liposomes with the antigen. Extensive immunoglobulin adsorption suggests caution in interpreting covalent linkage values obtained upon prolonged incubation of chemically modified antibodies with liposomes. It may also be a preferred alternative in preparing targeted liposomes for intravenous use when chemically modified antibodies promote premature clearance of the antibody-liposome complex from the circulation.
The aims of this study were to elucidate further the role of histamine in the rat uterotrophic response and to investigate the differences between the oestrogen and the anti-oestrogen induced uterine responses. The parameters examined were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights. 17 beta-Oestradiol and the anti-oestrogen, tamoxifen, were used to stimulate the ovariectomised rat uterus and the antihistamines mepyramine (H1) and ranitidine (H2) were employed to modify these responses. The uterine changes evoked by oestradiol proved to be more susceptible to modification by the antihistamines than the tamoxifen-stimulated responses. The results suggest that histamine is involved in the early uterine response to oestradiol but histamine does not appear to play a major role in the uterine response to tamoxifen.
Pretreatment of mature ovariectomized rats with DL-5 alpha-difluoromethylornithine (DFMO) inhibits the 6-h uterine blood flow response to oestradiol and also depresses the stimulatory effect of oestradiol on wet and dry uterine weight. Results from this study indicate that polyamine synthesis is implicated in the uterine response to oestrogen.
The previously established direct relationship between long half-life of uncharged small unilamellar liposomes in the circulation of injected animals and reduced permeability to entrapped solutes in the presence of blood plasma was investigated further. It was found that vesicle size and surface charge override state of membrane permeability in determining rates of vesicle clearance. Thus, half-lives of liposomes that were practically impermeable in plasma were much shorter for larger vesicles or vesicles with a negative charge on their surface. 111In-labelled bleomycin-containing small unilamellar liposomes with long half-lives accumulated in the liver after injection to a much lesser extent (e.g., 26%) than similar liposomes (55% of the dose) exhibiting a shorter half-life. Much of the injected long-lived liposomes (about 35%) were recovered in the carcass of the animals. Scanning of the carcasses revealed quantitative accumulation of radioactivity in the bones, presumably the phagocytic cells of the bone marrow. Long-lived liposomes appear suitable for drug delivery to, or imaging of the bone marrow.
The rapid transit system for patients with fractures of the proximal femur consists of immediate internal fixation or replacement of the fractured bone under spinal anaesthesia, without any sedation. Patients are mobilised within hours of surgery and sent home as soon as they can walk. They are supervised at home by both an experienced physiotherapist and a visiting nurse. Sixty nine patients admitted to a metropolitan teaching hospital were considered for the system and 50 were accepted. Their age distribution and level of general ill health were comparable with those in other series. The rapid transit system resulted in 90% of patients accepted being discharged to their homes within the first five days, with a lower morbidity and a mortality at three months of 7%. Using the rapid transit system rehabilitation in the original environment is difficult only if the patient lives alone, and even then temporary support is often enough to allow them to return home.
A 28-year-old man with a history of Crohn's disease presented with right pleuritic pain and dyspnea. Chest radiography showed a right pleural effusion. Thoracocentesis yielded purulent fluid that subsequently grew Enterobacter aerogenes. Computed axial tomography of the abdomen revealed right subphrenic abscess and right hepatic lobe abscess. Antibiotic therapy and surgical drainage resulted in complete recovery. A review of the English literature produced 18 cases of liver abscess complicating Crohn's disease. Details of 14 of these cases are summarized.
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The effect of high density lipoproteins (HDL) on the stability and clearance of injected liposomes was investigated under conditions of abnormal lipoprotein metabolism in vivo. Small unilamellar liposomes composed of phosphatidylcholine and containing quenched carboxyfluorescein were injected intravenously or intraperitoneally into normal mice or mice previously made lipoprotein deficient with 4-aminopyrazolo[3,4d]pyrimidine (4-APP). As evidenced from quenched carboxyfluorescein values in the blood, levels of stable liposomes in the circulation were increased and clearance rates reduced considerably in lipoprotein-deficient animals indicating increased bilayer integrity. This was confirmed by the demonstration that transfer of liposomal phosphatidylcholine to HDL, occurring in the presence of normal mouse plasma, was virtually abolished in the presence of plasma from lipoprotein deficient mice. The role of other lipoprotein species in destabilizing liposomes was also investigated. Plasma from lipoprotein-deficient mice was supplemented with increasing amounts of HDL, LDL + IDL or VLDL (to cover the physiological range of lipoprotein concentrations in mouse blood) prior to the addition of phosphatidylcholine liposomes, and incubated at 37 degrees C. It was shown that among the lipoprotein species studied only HDL was detrimental to liposomal stability under the conditions employed. Our results indicate that use of liposomal drugs in the treatment of patients must take into account HDL fluctuations in their blood as these could after liposomal membrane permeability to the drugs and thus upset therapeutic efficiency.
The fate of small (30-60 nm) and large (about 400 nm diameter) liposomes composed of phosphatidylcholine or sphingomyelin and equimolar cholesterol and containing quenched carboxyfluorescein and 111In-labelled bleomycin after footpad injection of rats was investigated. Judging from the values of latent carboxyfluorescein in the plasma, phosphatidylcholine and sphingomyelin small liposomes entered the blood circulation intact, presumably via the lymphatics to reach 3 h after injection a peak of 16.9 and 23.1% of the dose per total blood, respectively. Of the 111In radioactivity given in phosphatidylcholine liposomes, about 32% was recovered in the liver. Hepatic uptake of 111In for sphingomyelin liposomes was lower (about 9%) reflecting their slower rate of clearance. No latent carboxyfluorescein could be detected in the blood after injection with phosphatidylcholine or sphingomyelin large liposomes and levels of 111In in the liver (and spleen) were very low. A proportionally much greater amount of liposomal 111In was intercepted by the popliteal and to a lesser extent, the lumbar lymph nodes. Such uptake was significantly higher (e.g. 463%) for small than for large (e.g. 195% per g popliteal nodes) liposomes. After foot pad injection of large liposomes into Walker 256 tumour-bearing rats, localization of 111In in the popliteal nodes was similar to that seen with control animals. However, 111In localization in the lumbar nodes was augmented more than 5-fold. These results suggest that large liposomes as used in this study, characterized by efficient drug entrapment, inability to reach the liver and spleen and improved localization in the lymph nodes of tumour-bearing animals may be preferable to vesicles of small size for the local treatment of lymphatic metastases.
Relationships between perinatal mortality, disrupted utero-placental function and prostaglandin metabolism have been studied in Zn-deficient rats. Uterine contractility in vitro, placental blood flow in vivo, and uterine and placental prostaglandin synthesis from [1-14C] arachidonic acid in vitro were investigated at day 22 of pregnancy. High amplitude uterine contractions were almost completely eliminated and utero-placental blood flow was decreased by 85% by Zn deficiency. Synthesis of [1-14C]-prostaglandin E2, F2 alpha and 6-keto-F1 alpha from [1-14C] arachidonic acid decreased significantly in uterine tissue but increased in placentae. These possibly inter-related effects may contribute to the high perinatal mortality observed in Zn deficiency.
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Oestradiol (single injection) resulted in a peak in uterine blood flow 3 h later with a secondary rise in blood flow at 30 h. Uterine wet and dry weights increased more slowly and were still above control values 24 h after the injection. If a second injection of oestradiol was given 24 h after the first then uterine blood flow was again maximal at 3 h but remained at this level for a further 3 h, probably due to the secondary rise induced by the first injection. Uterine wet weight was further increased by the second injection of oestradiol but the effect did not occur until 6 h after the oestrogen treatment. Pretreatment with an anti-oestrogen, tamoxifen or nafoxidine, inhibited or reduced significantly the uterine weight and uterine blood flow responses to oestrogen but increased uterine weights and produced some increase in uterine blood flow when given alone. It is suggested that both blood flow and weight responses to oestrogen in the uterus are mediated through the oestrogen receptors.
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