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Biomedical subjects

P Andrews

Publications and source records attributed to P Andrews.

At least 19 recordsLinked to original sources

Evolution and environment in the Hominoidea.

Between 10 and 20 million years ago, a variety of hominoid primates lived in Africa, Europe and Asia. The question of which of these, if any, lie closest to the ancestries of humans and modern apes remains a lively source of debate. Recent fossil discoveries, though, shed light on the environments in which the various groups of hominoid emerged and, it is hoped, on their evolution. But the lack of a hominid fossil record before about 5 million years ago--and any fossil record for the African apes--is still a frustrating barrier.

Animals

Helicobacter pylori eradication with doxycycline-metronidazole-bismuth subcitrate triple therapy.

Triple therapy containing tetracycline HCl is currently among the most efficient combination therapies for eradication of Helicobacter pylori. Substitution of doxycycline for tetracycline HCl offers advantages of less frequent dosing and extrarenal excretion. In this study patients with duodenal ulcer or non-ulcer dyspepsia positive for H. pylori were randomized to either doxycycline or tetracycline HCl triple therapy in conjunction with bismuth subcitrate and metronidazole. Of the 34 patients taking doxycycline, only 22 (65%) achieved H. pylori eradication at the 4-week rebiopsy, compared with 36 of 39 (92%) taking tetracycline HCl (p = 0.004). We conclude that doxycycline-containing triple therapy is less effective for H. pylori eradication and offers no clinical advantage over tetracycline HCl-containing triple therapy.

Adult

Advances in the treatment of acquired and developmental defects of hard dental tissues.

With the decline in dental caries, the dental profession and the general public have become sensitized to the "new" specialty of cosmetic dentistry. As a consequence, research in the field of dental materials for the ideal, most natural restorative materials and techniques has become a primary focus and has had a profound influence on dental education and practice. This brief article will highlight some of these newer concepts.

Composite Resins

Smoking does not contribute to duodenal ulcer relapse after Helicobacter pylori eradication.

Cigarette smoking is believed to be one of the major factors influencing duodenal ulcer (DU) recurrence. However, the influence of cigarette smoking on DU recurrence after the eradication of Helicobacter pylori has not been separately addressed. The aim of this study was to investigate DU relapse rate in smokers and nonsmokers, both with confirmed eradication of H. pylori. Patients with H. pylori eradication, demonstrated at endoscopy 4 wk post-treatment, were included in the study. Smoking history was obtained with a standard questionnaire, and patients were followed endoscopically, both yearly and at symptomatic recurrence, to detect anatomical DU recurrence. Of the 197 (121M:76F) patients enrolled in the study and followed for 1-6 yr, 80 (41%) were smokers, smoking 5-40 cigarettes/day. The 117 (59%) nonsmokers included 31 (26%) patients who had ceased smoking 4-20 yr ago. Another seven (9%) smokers ceased smoking during the follow-up period. In the 197 patients with eradicated H. pylori and cured DU, there has been no recurrence of ulcer, regardless of smoking status. We conclude that in patients with DU in whom H. pylori infection is eradicated, ulcer disease does not recur, as observed for up to 6 yr. Furthermore, cigarette smoking is not a risk factor for DU recurrence, provided H. pylori is eradicated.

Anti-Ulcer Agents

Helicobacter pylori-negative gastric ulcer.

Causes of Helicobacter pylori (HP)-negative gastric ulcers (GUs) have not previously been systematically studied. In this study we examined possible causes of HP-negative GUs. Among 115 consecutive patients with endoscopic diagnoses of GU, 71 (62%) had HP infection, and 44 (38%) were found to be HP-negative. Of the 71 HP-positive patients, 47 (66%) had no other detectable causal factors, 21 (30%) were regularly taking nonsteroidal antiinflammatory drugs (NSAIDs), and three (4%) had malignant GU. Of the 44 HP-negative patients, 29 (66%) were taking NSAIDs, two (5%) had a malignant GU, whereas 13/44 (30%) (11% of total 115) patients had no identifiable cause. These patients were classified as having "idiopathic GU." Some 38/115 (33%) GUs occurred on the lesser curve, and these were more often (p = 0.012) HP-positive (76%) than prepyloric GUs (60/115 (52%)). We conclude that although most patients have an identifiable cause of GU, around 11% will have no apparent contributing factor. HP-positive GUs are more frequently located on the lesser curve. It is now important to identify the cause of GU, because this may dictate choice of management.

Anti-Inflammatory Agents, Non-Steroidal

Radial keratotomy. II. Role of the myofibroblast in corneal wound contraction.

The cellular mechanism of corneal wound contraction after radial keratotomy (RK) was studied in a feline eye model. A total of 10 cat eyes were evaluated at various times from 0-30 days after surgery. Changes in the distribution of intracellular filamentous actin, nonmuscle myosin, alpha-actinin, surface membrane alpha 5 beta 1 integrin, and extracellular fibronectin were studied using immunofluorescence and laser confocal and electron microscopy. From day 3-7, staining for fibronectin increased along the wound margin. By day 7, keratocytes adjacent to the wound margin showed increased f-actin staining with intense staining for fibronectin compared with normal keratocytes. Myosin and alpha 5 beta 1 integrin expression was very weak at this time; alpha-actinin was not found. By day 14, fibroblasts within the wound formed f-actin microfilament bundles (stress fibers) which colocalized with fibronectin. Wound-healing fibroblasts also stained positively for alpha 5 beta 1 integrin, myosin, and alpha-actinin (the latter two were colocalized). The presence of myosin and alpha-actinin in the wound fibroblasts and the re-organization of f-actin into stress fibers by day 14 correlated with the development of wound contraction. A comparison of the cellular distribution of actin, myosin, and alpha-actinin with alpha 5 beta 1 integrin 14 days after injury suggested that integrin was localized along stress fiber bundles during wound contraction. The data from this study suggest that modulation of wound gape during healing of RK wounds may involve transformation of the corneal keratocyte to a myofibroblast-like cell and the subsequent formation of intracellular stress fibers composed of f-actin, nonmuscle myosin, and alpha-actinin. Based on the colocalization of fibronectin filaments and f-actin filaments and the unique distribution of alpha 5 beta 1 integrin, these findings support the hypothesis that the tension within the wound is generated by the formation of intracellular stress fibers and the interactions between stress fibers and the extracellular matrix, mediated by specific membrane receptor molecules.

Animals

Hominoid dietary evolution.

During the later Palaeocene and early Miocene, catarrhine primates and the evolving hominoids had adaptations for frugivorous diets, with the emphasis on soft foods. Early in the middle Miocene the hominoids underwent a major shift, both in morphology and in habitat, with the morphology characterized by thickened enamel on the molars, enlarged incisors and massive jaws. The diet indicated by this morphology is interpreted as still mainly frugivorous but with changed emphasis, possibly towards harder objects. The thick-enamelled hominoids are found associated with more open forest habitats, and the distribution of food resources in equivalent habitats today is discontinuous both in time and in space, leading to evolutionary pressures particularly affecting locomotion, brain size and social behaviour. The earliest known hominid fossils differed little in dental and mandibular morphology from the middle Miocene apes, and the implied dietary similarity, together with ape-like patterns of dental development and retained arboreal adaptations of the postcrania, suggests little change in the foraging strategies of the earliest hominids compared with their ape ancestors and further suggests similarity in evolutionary grade. This similarity may have extended to other aspects of behaviour, for example to patterns of tool making and use, which may have been similar in the common ancestor of apes and humans to the pattern shared by the earliest australopithecines and chimpanzees.

Animals

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence

Action spectrum of antiviral factor from chicken sera.

Rous sarcoma virus infections of regressor line chickens stimulate the transient production of antiviral factors in the serum. Earlier the present authors reported that a viral neutralization factor (VNF) inactivated Rous sarcoma virus during a 3-h incubation. The VNF is likely to have a broad antiviral and antimicrobial spectrum because it is active against several unrelated pathogenic poultry viruses. The present study measured the activity of VNF against Newcastle disease virus, infectious bursal disease virus, and infectious bronchitis virus. The VNF is active in immunologically incompetent systems and must be preincubated with the virus in order to inhibit it. Based upon the current experiments, it is proposed that VNF is not an immunomodulator but directly inactivates the virus. The VNF agent appears to be one of a newly identified class of nonspecific antiviral agents produced in vivo in chickens in response to a viral infection.

Animals

Helicobacter pylori-negative duodenal ulcer.

Most patients with chronic duodenal ulcer (DU) craters have gastritis associated with Helicobacter pylori (HP), now thought to be the major cause of DU. A smaller proportion of DU patients have no detectable HP. In this study, we examined the frequency and causes of HP-negative duodenal ulcers. In 302 consecutive patients with endoscopic diagnosis of duodenal ulcer, 284 (94%) were found to have associated HP gastritis, whereas 18 (6%) were HP-negative on histology, culture, and urease test. The largest subgroup of HP-negative patients (8/18) was made up of those who had been taking nonsteroidal antiinflammatory drugs (NSAIDs), followed closely (4/18) by patients with recent intake of antibiotics. Causes of DU in the remaining subgroups included two patients with duodenal Crohn's disease, two with Gastrospirillum hominis infection, one with penetrating carcinoma of the pancreas and one with no detectable cause. We conclude that, although the most common causal factor of duodenal ulcer is HP, some 6% of DU's will be HP-negative, signaling unusual etiology. It is now important to identify the cause of duodenal ulcer so as to initiate appropriate therapy.

Adult

Cure of duodenal ulcer after eradication of Helicobacter pylori.

Eighty-two patients, whose duodenal ulcers were recurrent or resistant to H2-receptor antagonist therapy, were entered in a treatment protocol of ranitidine followed by a four-week "triple therapy" course to eradicate Helicobacter pylori (HP) infection. The triple therapy consisted of colloidal bismuth subcitrate, tetracycline and metronidazole. Duodenal ulcer healed in all 78 patients available for endoscopy and H. pylori infection was shown to be eliminated in 75 patients (96%) at rebiopsy four weeks after cessation of therapy. In these 75 remaining patients the relapse rates for H. pylori infection and duodenal ulcer were studied endoscopically, yearly and at any recurrence of symptoms. At Year 1, 71 of 73 patients remained free of H. pylori infection (HP-negative) and duodenal ulcer. The corresponding figures subsequently were: Year 2, 57/57; Year 3, 34/34; Year 4, 15/15. No duodenal ulcers recurred in HP-negative patients who were followed for up to four years. Two patients of the original cohort of 75 HP-negative patients were HP-positive with endoscopic duodenitis at 12 months, and one at 36 months, but all were without reulceration. Distorted duodenal caps gradually returned to near-normal appearance in 80% of patients by two years. From this four-year follow-up study we conclude that duodenal ulcer disease will not recur provided the patient remains free of H. pylori.

Adult

Zonal unit-gravity elutriation. A new technique for separating large cells and multicellular complexes from cell suspensions.

A new and simple technique, zonal unit-gravity elutriation, has been devised for separating very large cells, multicellular complexes, or small organisms from suspensions consisting mainly of small cells. The separation vessel is a conical chamber with an entrance at the lower, narrower part of the cone and an exit at the upper, wider part of the cone via a dome-shaped lid. A baffle at the entrance prevents turbulence from incoming fluid. Chambers of differing widths and wall slopes are chosen depending on the sedimentation rate of the particles to be separated. A small volume of the cell suspension is placed in the chamber on the bench in a cold-room. Medium stabilized by a shallow density gradient is pumped into the base of the chamber and ascends, creating a decreasing velocity gradient. Cells sediment at unit-gravity against this ascending counterstream, and are separated into bands according to sedimentation velocity. By adjusting the flow rate of the medium, different sizes of cells can be separated. Tumor cells can be enriched, and larger blast cells can be separated from small cells in lymphoid cell suspensions. The procedure produces complete separation of thymic nurse cells (epithelial-lymphoid complexes) from free thymocytes in digested thymus suspensions and produces substantial enrichment of thymic rosettes (macrophage-lymphoid complexes). A very favorable situation for applying this technique is the isolation of Taenia taeniaformis larvae, which can be completely purified from infected liver suspensions, representing a 4 X 10(5)-fold enrichment of the parasites, with high recovery, in a single 30 min operation.

Animals

Hydrophobic esters of cellulose: properties and applications in biochemical technology.

We have investigated the utility for enzyme immobilization of several hydrophobic cellulose esters, as a function of solvent composition, extent of esterification, and enzyme. Phenoxyacetyl cellulose was also used for immobilization of rat liver microsomes, hydrophobic chromatography of proteins, and removal of Triton X-100 from protein solutions. Phenoxyacetyl groups esterified to cellulose were much less subject to enzymatic hydrolysis than soluble phenoxyacetyl esters.

Binding Sites

The effect of praziquantel on Hymenolepis diminuta in vitro.

Qualitative observations were made on Hymenolepis diminuta, H. microstoma, H. nana and pre-adult Echinococcus multilocularis in vitro. A dose as low as 0.0001 microgram praziquantel/ml affects the tapeworms, while concentrations of 0.01 - 0.1 and 1-10 microgram/ml cause contraction and paralysis in the contracted state within 10 min and 10-30 s, respectively. The in vitro effects of praziquantel on Hymenolepis diminuta have been studied using anaerobic and aerobic incubations and media containing or lacking glucose. Praziquantel inhibits glucose up-take by half at a concentration of 0.1 microgram/ml, both under anaerobic and aerobic conditions. The stimulation of lactate release was most marked in the absence of glucose. A doubling of the amount of lactate released during anaerobic incubation in the presence of glucose was achieved in 0.1 microgram/ml, while 0.01 microgram/ml had the same effect in the absence of glucose. Under aerobic conditions and in the absence of glucose, 0.1 microgram/ml doubled the amount of lactate released while 3 and 10 microgram/ml were without effect in the presence of glucose. Praziquantel increases the total amount of excreted acidic metabolites only in the absence of glucose. The oxygen consumption of H. diminuta was unaffected by praziquantel at a concentration of 10 microgram/ml. Worms treated in their host and then incubated display the same changes as worms treated in vitro. Praziquantel causes an efflux of glucose and alpha-amino-N from the worm into the medium. This impairment of tegumental integrity and the inhibition of glucose up-take and the stimulation of lactate release are reversible after a 15 min incubation in praziquantel solution. Discussion of pharmacokinetic data indicates, that in the in vivo situation, effective concentrations of praziquantel prevail for much longer. Mechanisms that might explain the observed effects are discussed.

Aerobiosis