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Biomedical subjects

A Richardson

Publications and source records attributed to A Richardson.

At least 199 records · Page 11Linked to original sources

A national study to monitor the safety of IUCD use.

OBJECTIVE: To determine whether the known adverse effects of IUD use were being kept to a minimum in a population of women. DESIGN: A national survey of all doctors purchasing IUDs in a three-month period. Information was sought on the doctors' training, experience and usual insertion practice, and also on characteristics of each woman receiving an IUD in the study period. MAIN OUTCOME MEASURES: Published national and international guidelines on selection of users for IUDs and on training for IUD insertion were compared with our findings on these measures. RESULTS: Not all IUD insertions were in accordance with published guidelines. Very few IUD insertions (0.9%) were carried out in the face of absolute contraindications to this type of contraception. However, 126 insertions (27%) were for women who had a relative contraindication, excluding an incomplete family. Gynaecologists were significantly less likely to fit an IUD in the presence of contraindications than other doctors. Few doctors reported training to the standard recommended. CONCLUSIONS: That the known adverse effects of IUD use are not being kept to a minimum for New Zealand women. The study design could be used to estimate the potential for adverse effects in populations for other types of contraceptives.

Adolescent↗

Effect of dietary restriction on DNA repair and DNA damage.

Dietary restriction is the only experimental manipulation known to extend lifespan and retard aging in mammals. Therefore, it is a powerful tool for identifying cellular processes that are involved in aging and senescence. Recently, several laboratories have begun to examine the effects of dietary restriction on the integrity of the genome and the ability of cells to repair DNA. In most studies, it was found that the repair of DNA damage, as measured by unscheduled DNA synthesis, was significantly higher in cells isolated from rodents fed calorie-restricted diets compared to cells isolated from rodents fed ad libitum. Dietary restriction also was observed to be associated with a reduction of the levels of certain types of DNA damage; however, preliminary experiments suggest that the effect of dietary restriction on the age-related accumulation of DNA damage depends on the type of DNA damage studied.

Animals↗

Lower third molar development subsequent to second molar extraction.

Development and eruption of lower third molars was examined in 63 subjects who were treated by extraction of second molars. Changes in mesiodistal and buccolingual lower third molar angulation were measured on 60 degrees cephalograms taken before extraction and 3 or more years later. The final position of lower third molars was assessed on models at the end of the observation period by using a scoring system. All lower third molars erupted in periods ranging from 3 to 10 years after extraction. Ninety-nine percent of the third molars upright mesiodistally, but few became as upright as the second molars they replaced. Model analysis showed that 96% of the lower third molars erupted in good or acceptable positions.

Adolescent↗

The effect of extraction of four second permanent molars on the incisor overbite.

Changes in incisor overbite were compared in 33 subjects who had four second molars extracted and 33 untreated subjects. There was an average increase in overbite of 0.7 mm in the extraction group, significantly different from an average decrease of -0.8 mm in the control group. The tendency to increase in overbite was greater in subjects whose presenting overbite was already reduced. The mechanism responsible for overbite reduction appeared to be a slight distal movement of the dentition, with retroclination of incisors and increase in inter-incisal angle.

Adolescent↗

Early treatment of Class III incisor relationship using the chincap appliance.

Twenty-three patients (10 male, 13 female), with Class III relationships of the incisor teeth at the mixed dentition stage, were treated with the chincap appliance associated, where appropriate, with an upper removable appliance to procline upper incisors and to free the occlusion. Cephalometric analyses at the beginning and at the end of active treatment were compared with those in a carefully matched untreated control group selected from the Belfast Growth Study. At the beginning of treatment patients differed significantly from the controls in the SNB was larger, ANB was negative, Wits' analysis was negative, and the intermaxillary angle significantly reduced. The overjet was reversed, the lower incisors were ahead of A-Po, and the upper lip was far behind the E line. Significant changes brought about by the treatment were improvement in the Wits' relationship (but there was no significant change in the ANB angle), increases in the intermaxillary angle and lower facial height, improvement in the overjet, proclination of upper incisors and retroclination of lower incisors, backward movement of the lower incisors in relation to A-Po, and backward movement of the lower lip. The efficacy of the chincap appliance can be attributed to retroclination of lower incisors and downward movement of the mandible which may improve the jaw relationship without affecting the ANB angle. There were marked changes in the lip posture.

Case-Control Studies↗

The effect of age on the synthesis of two heat shock proteins in the hsp70 family.

Hepatocytes isolated from male F344 rats were exposed to elevated temperatures (40 degrees C to 45 degrees C), and the incorporation of [35S]-L-methionine into proteins was measured from fluorograms of two-dimensional polyacrylamide gels. The synthesis of two proteins was induced by temperatures of 40 degrees C to 42.5 degrees C; however, 45 degrees C inhibited the synthesis of all proteins. Based on their apparent molecular weights and pI values and their recognition by a monoclonal antibody to the HSP70 gene family, the two proteins induced by hyperthermia were found to be the highly heat-inducible hsp70 and the constitutive hsc70. Because a heat shock of 42.5 degrees C for 30 minutes had very little effect on cell viability and induced the synthesis of hsp70 and hsc70, this heat shock was used to study the effect of age on the ability of hepatocytes to respond to the stress of hyperthermia. Neither hepatocytes isolated from young adult (5-7 months) nor old (25-27 months) rats synthesized detectable amounts of hsp70 when incubated at 37 degrees C. However, heat shock induced the synthesis of both hsp70 and hsc70 in hepatocytes isolated from young adult and old rats. The induction of hsp70 synthesis was significantly lower (37%) for hepatocytes isolated from old rats compared to hepatocytes isolated from young adult rats. However, neither the basal level nor the induced level of hsc70 synthesis changed significantly with age. Thus, aging resulted in a decrease in the ability of hepatocytes to synthesize hsp70 in response to hyperthermia; this effect, however, was specific for hsp70.

Actins↗

Variation in expression of endothelial adhesion molecules in pretransplant and transplanted kidneys--correlation with intragraft events.

Endothelial adhesion molecules are directly involved in the localization and migration of leukocytes from the circulation into tissues at sites of inflammation. We have compared the expression of PECAM-1 (CD31), ELAM-1, ICAM-1 (CD54), and VCAM-1 in pretransplant (n = 20) and needle-core biopsies from renal transplants obtained during different clinical circumstances (n = 42). PECAM-1 was consistently expressed on all endothelium in both pretransplant and transplant biopsies. In contrast, there was variation in endothelial expression of ELAM-1 and in proximal tubular expression of ICAM-1 and VCAM-1 between pretransplant biopsies. After transplantation induced expression of endothelial ELAM-1 and VCAM-1 and tubular induction of ICAM-1 and VCAM-1 was detected. Induced adhesion molecule expression was frequently associated with focal leukocyte infiltration, and there was a significantly higher level of CD45 and CD25 positive cell infiltration in biopsies with induced adhesion molecule expression. The induction of adhesion molecule expression is evidence of endothelial activation in these transplant biopsies. Comparison of adhesion molecule expression and HLA-class II antigen expression revealed that induced tubular class II antigens may be detected in the absence of induced adhesion molecule expression.

Antigens, Differentiation, Myelomonocytic↗

Expression of heat shock protein 70 is altered by age and diet at the level of transcription.

Because heat shock proteins have been shown to play a critical role in protecting cells from hyperthermia and other types of physiological stresses, it was of interest to determine what effect age and caloric restriction have on the ability of cells to regulate the expression of heat shock protein 70 (hsp70), the most prominent and most evolutionarily conserved of the heat shock proteins. Caloric restriction is the only experimental manipulation known to retard aging and increase survival of mammals. The ability of hepatocytes isolated from young/adult (4- to 7-month-old) and old (22- to 28-month-old) male Fischer F344 rats fed ad libitum or a caloric restriction diet (60% of the content of the ad libitum diet) to express hsp70 was determined after a mild heat shock (42.5 degrees C for 30 min). We found that the induction of hsp70 synthesis and mRNA levels by heat shock was 40 to 50% lower in hepatocytes isolated from old rats than in hepatocytes isolated from young rats. Using in situ hybridization, we found that essentially all hepatocytes from the young/adult and old rats expressed hsp70 in response to heat shock; therefore, the age-related decrease in the induction of hsp70 expression was not due to an age-related accumulation of cells that do not respond to heat shock. Measurements of hsp70 mRNA stability and hsp70 transcription demonstrated that the age-related decline in hsp70 expression arose from a decline in hsp70 transcription. Interestingly, the age-related decline in the induction of hsp70 expression was reversed by caloric restriction; e.g., the induction of hsp70 synthesis, mRNA levels, and nuclear transcription were significantly higher in hepatocytes isolated from old rats fed the caloric restricted diet than in hepatocytes isolated from old rats fed ad libitum. The levels of the heat shock transcription factor in nuclear extracts isolated from heat-shocked hepatocytes were measured in a gel shift assay. Binding of the heat shock transcription factor to the heat shock element decreased with age and was significantly higher in hepatocyte extracts isolated from old rats fed the caloric restriction diet than in those from old rats fed ad libitum. Thus, our study demonstrates that the ability of hepatocytes to respond to hyperthermia and express hsp70 decreases significantly with age and that this decrease occurs at the transcriptional level. In addition, caloric restriction, which retards aging, reversed the age-related decline in the induction of hsp70 transcription in hepatocytes.

Aging↗

Guanine nucleotide-binding protein-coupled and -uncoupled states of opioid receptors and their relevance to the determination of subtypes.

Opioid receptors are currently classified as mu, delta, and kappa types, but various subtypes have also been proposed. We have investigated whether subtypes exist by using [3H]bremazocine. [3H]Bremazocine binds to twice as many naloxone-sensitive sites as other nonselective opioid agonists, as shown in four membrane types that have very different ratios of mu, delta, and kappa receptor types. [3H]Bremazocine binding is completely inhibited by an excess (in unlabeled form) of other opioid ligands, with Hill coefficients of 0.8-0.95. These paradoxes can be explained if there are high- and low-affinity states of the mu, delta, and kappa receptors and bremazocine binds with similar affinities to both states. We propose that these states are the guanine nucleotide-binding protein (G-protein)-coupled form and the uncoupled form of each receptor. As evidence for this proposal, the [3H]bremazocine binding suffered little or no loss with G-protein-uncoupling treatments, whereas binding of other opioid agonists was fully sensitive. We conclude that [3H]bremazocine offers a tool for the measurement of the total pools of coupled and uncoupled opioid receptors and that much of the previous characterization of opioid receptor subtypes reflects, instead, a significant pool of G-protein-uncoupled opioid receptors.

Analgesics↗

Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have few and apparently random mutations. However, in this study, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03% in B-CLLs whereas the somatic mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in CLLs is particularly prevalent, and interchanges in CDRs often lead to acquisition of charge. Analysis of somatic mutations and mutations to charged residues demonstrated that the mutations in CLLs are highly selected.

Adult↗

Prolonged exposure to inositol 1,4,5-trisphosphate does not cause intrinsic desensitization of the intracellular Ca(2+)-mobilizing receptor.

The rapid release of Ca2+ from intracellular stores stimulated with inositol 1,4,5-trisphosphate (InsP3) has required superfusion or stopped-flow techniques to resolve the kinetics of Ca2+ mobilization and made it difficult to determine whether the InsP3 receptor desensitizes during prolonged stimulation. Here we have overloaded the intracellular Ca2+ stores of permeabilized rat hepatocytes by incubating them with ATP and 45Ca2+ in the presence of pyrophosphate, which precipitates Ca2+ within the lumen of the stores. Subsequent ATP removal initiated slow 45Ca2+ efflux that followed zero-order kinetics, allowing us to examine the effects of InsP3 over a prolonged time course. InsP3 produced a concentration-dependent increase in the 45Ca2+ efflux rate that was sustained for several min. The rate rapidly returned to the unstimulated level after the addition of decavanadate, a competitive antagonist of InsP3 at its receptor. Prior incubation with a submaximal concentration of InsP3 (1 microM) did not affect the subsequent enhanced rate of 45Ca2+ efflux stimulated by a higher, but still submaximal, concentration of InsP3 (3 microM). We conclude that prolonged exposure to InsP3 does not desensitize the InsP3 receptor and that intrinsic receptor desensitization cannot provide an explanation for the quantal responses to InsP3 observed in several cell types.

Animals↗

Talking positive.

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Acquired Immunodeficiency Syndrome↗

Protection by opioid ligands against modification of the opioid receptor by a carbodiimide.

Opioid receptors in membranes prepared from guinea-pig cerebellum were modified irreversibly by treatment with a water soluble carbodiimide, 1-ethyl,3-(3-dimethylaminoethyl)carbodiimide (EDAC). This decreased the number of [3H]bremazocine binding sites (Bmax reduced from 140 to 100 fmol/mg by 1 mM EDAC) without changing their affinity. When the EDAC concentration used was sufficient (500 mM) to inactivate almost all of the opioid receptors, the modification was partly prevented by inclusion of high concentrations (100 microM) of opioid agonists ([D-Ala2, MePhe4, Glyol5]-enkephalin, [D-Ala2, D-Leu5]-enkephalin,(+)-trans-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzo(b)thiophene-4-acetamide hydrochloride), although they exhibited equal efficacy irrespective of their mu, delta or kappa type selectivity. However, almost all of the opioid binding sites were protected when a guanine nucleotide analogue (GppNHP, 100 microM) was also included with the agonists during carbodiimide treatment.

Animals↗

Public opinion and purchasing.

OBJECTIVES: To explore the use of a questionnaire to obtain representative public opinions on health services. To examine residents' priorities, knowledge, and views on the public's role in decision making. DESIGN: Self administered postal questionnaire. POPULATION: Random sample of 1500 residents in Bath District Health Authority, drawn from electoral registers. MAIN OUTCOME MEASURES: Levels of agreement or disagreement with statements provided and degree of importance given to services and aspects of services. RESULTS: 70 questionnaires were returned unopened. Completed questionnaires were returned by 704 (49.2%) of the 1430 remaining residents. Kidney dialysis was thought very important by 559 (87%) respondents and family planning by only 58 (9%). Public priorities did not seem to reflect value for money. Clear information about treatment was rated as very important by 530 (76%) and comfortable waiting areas by 70 (10%). 372 (53%) of respondents said that they would definitely travel to a hospital outside the district to reduce their wait for surgery. Knowledge of the services provided by the authority and the money available to it was poor. 446 (65%) respondents wanted greater public involvement in decision making. CONCLUSIONS: A postal questionnaire can provide useful information about public priorities and perceptions about the services provided. More information about health services and their costs and benefits should be given to the public to assist greater public participation in decision making.

Community Participation↗

Chronic pancreatitis beginning in childhood and adolescence.

We identified 10 patients with symptoms beginning before the age of 20 years in a group of 69 patients with proven chronic pancreatitis. Six of the 10 patients were women. There was a family history of pancreatitis in three patients and alcohol exposure in seven patients. Three patients were dependent on narcotics at the time of presentation. Six of the 10 patients had pancreatic duct dilatation to 10 mm or more in diameter during observation. These six patients underwent pancreaticojejunostomy, with clinical improvement in five patients. The median time of follow-up was 19 years from presentation. No patient developed diabetes and one developed malabsorption. Only three patients were free of pain, but four other patients had only mild episodes that rarely required hospital admission. One patient died of metastatic abdominal carcinoma of unknown origin 51 years after developing familial pancreatitis. Chronic pancreatitis beginning at a young age is sufficiently common to merit special awareness. It is compatible with prolonged survival, and pancreaticojejunostomy may help if the pancreatic duct reaches sufficient size. The disease does not seem to burn out with time.

Adolescent↗

Studies exploring self-care for the person coping with cancer treatment: a review.

Individuals living with an illness such as cancer and receiving chemotherapy must often meet a new set of demands, that are not amongst their usual repertoire of skills and knowledge. Little is known about how patients manage the illness of cancer and in particular what self-care actions they develop and perform to cope with the side-effects of treatment. This paper outlines Orem's theory of self-care and describes its utilization in the design of a number of research studies in the cancer patient population. In particular, work which has explored the role of self-care in relationship to the control of chemotherapy induced nausea and vomiting is reviewed. The role of manipulating food and fluid intake, exercise and sleep and diversionary activities are explored; self-care is considered a vital part of the battle against combating nausea and vomiting induced by chemotherapy and further studies are urged.

Adaptation, Psychological↗