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Biomedical subjects

K Wright

Publications and source records attributed to K Wright.

At least 145 records · Page 8Linked to original sources

QALYS and long-term care for elderly people in the UK: scales for assessment of quality of life.

QALYs have developed in the UK as a tool for comparing the outcome of health care procedures in a single index over time. This tool can then be used, along with information on costs of procedures, in decision-making about health service resource allocation. It is shown that the attributes of disability and distress, on which QALYs are presently based in the UK, are insensitive to changes in the health status of elderly people in long-term care when compared to other measures of quality of life which are frequently used in studies of older people. Thus, if the use of QALYs increases, they should be based on attributes appropriate to the groups studied, otherwise certain groups may be discriminated against in health service resource allocation owing to the use of an insensitive measure of outcome.

Aged↗

A rat histone H4 gene closely associated with the testis-specific H1t gene.

A rat histone H4 gene closely associated with the testis-specific H1t gene was isolated by screening the Sargent-Bonner rat genomic library using cloned human histone genes as probes. Both the H4 gene and the H1t gene are located on a 7-kb EcoRI genomic DNA fragment. Although the deduced amino acid sequence of the rat H4 histone is identical to that of the sequence of human histone H4, the nucleotide sequence of the coding region differs significantly from the coding region of the human H4 gene. Moreover, the relative spacing between the 5'-consensus sequence elements is unique for an H4 gene. S1-nuclease protection analyses reveal that both the H4 and H1t mRNA species are present in a fraction of rat testis cells highly enriched in pachytene spermatocytes, while only the H4 mRNA species is present in a rat myeloma cell line (Y3-Ag1.2.3). During a 1-h hydroxyurea treatment of the Y3 cells, which produces a 99% inhibition of DNA synthesis, the level of this H4 mRNA drops by only 50%, indicating that the stability of this mRNA is only partially coupled with DNA synthesis.

Amino Acid Sequence↗

Identification of a novel calcium-binding protein (CP22) in multidrug-resistant murine and hamster cells.

Analysis of cytoplasmic extracts of multidrug-resistant murine and hamster cells by SDS gel and 2D gel electrophoresis showed that they expressed an abundant 22 kDa protein which was absent from the drug-sensitive parent lines. SDS gel electrophoresis in the presence of EGTA and direct binding tests with 45Ca2+ showed that the resistance-associated protein is a specific calcium-binding protein. Thus the development of multidrug resistance in both colchicine-selected hamster cells and adriamycin-selected murine cells is associated with a major change in calcium metabolism. These observations provide the first molecular basis for the hypothesis that Ca2+ plays a central role in the development of the multidrug resistance phenomenon.

Animals↗

Cell cycle-dependent expression of a stable episomal human histone gene in a mouse cell.

We have constructed a recombinant plasmid that includes a cell cycle-dependent human H4 histone gene with 650 base pairs of 5' and 900 base pairs of 3' flanking sequences and the 69% transforming fragment of bovine papilloma virus. When transfected into C127 mouse cells, this plasmid is maintained as a stable episome with approximately 20 copies per cell. Micrococcal nuclease digestion indicates that the episomal human histone gene is packaged as chromatin. The human H4 histone transcript is initiated at the correct 5' start site and undergoes selective destabilization when DNA synthesis is inhibited. When C127 cells containing the episomal H4 histone gene are synchronized, the human H4 histone mRNA levels are regulated coordinately with DNA replication and parallel those of transcripts from the murine chromosomal H4 histone genes. Our results suggest that the regulatory sequences and/or regulatory molecules associated with murine and human histone genes are compatible. The human histone gene-bovine papillomavirus episome is therefore a viable system for studying cell cycle-regulated histone gene expression under conditions where control is not influenced at the site of chromosomal integration by cis-acting elements of genes normally not contiguous.

Animals↗

Determining value for money in day hospital care for the elderly.

This paper describes how a prospective evaluation of the costs and effectiveness of day hospital care for the elderly and its alternatives could be undertaken. The number of day hospitals for the elderly has grown from zero to slightly over 300 in just over 20 years. Despite this there is no study in the existing literature which gives an indication of whether day hospitals provide a reasonable return on this substantial investment. The best way of determining whether day hospitals are a better investment than alternative modes of care would be a randomized controlled trial involving comparison of subgroups of day hospital patients against similar subgroups utilizing alternative modes of care, the costing of each patient's consumption of services within the treatment mode in which they commence the study plus any subsequent use of other services over a predetermined time period, the collection of clinical, social and psychological outcome data (including data on dependency) for each subgroup before, during and at the end of the study period, and some measure of patients' and relatives' satisfaction with the treatment received.

Aged↗

Chance discovery of multiple personality disorder in a depressed patient by amobarbital interview.

Although the diagnosis of multiple personality disorder (MPD) has been receiving renewed interest in the literature, it presents a number of clinical problems and challenges. A case study is reported in which this diagnosis was uncovered by chance during an amobarbital interview on a psychotically depressed young male patient. The patient had previously been only minimally responsive to pharmacotherapy for a major depressive episode with mood-congruent psychotic features. When the multiple personality disorder was diagnosed, treatment emphasis shifted toward psychotherapeutic modalities with marked clinical improvement. Several unique aspects of the case, including diagnostic methodology, results of serial dexamethasone suppression tests, and psychosomatic symptomatology, are discussed as well as the implications of this case within a larger clinical context.

Adult↗

Inferior vena caval stent filter.

New inferior vena caval filters for percutaneous placement were made by attaching filter wires similar to those in the bird's nest inferior vena caval filter onto expandable metallic stents. These stents formed a base on which to anchor the filter to the wall of the inferior vena cava. The stent filter can be introduced through a 12- to 13-French catheter sheath system. The system was successfully tested in 13 dogs.

Animals↗

Cerebral effects of hypocapnia plus nitroglycerin-induced hypotension in dogs.

This study examined the effect of hypocapnia (PaCO2 20 mm Hg) on cerebral metabolism and the electroencephalogram (EEG) findings in 12 dogs during nitroglycerin (NTG)-induced hypotension. Previous studies suggest that NTG is a more potent cerebral vasodilator than sodium nitroprusside or trimethaphan. It was speculated that combining hypocapnia with NTG-induced hypotension would cause less disturbance of cerebral metabolism and the EEG than the disturbances previously reported when hypocapnia was combined with hypotension induced by sodium nitroprusside or trimethaphan. All 12 dogs were examined at 1) normocapnia with normotension; 2) hypocapnia with normotension; and 3) hypocapnia combined with NTG-induced hypotension to mean arterial blood pressure (MABP) levels of 60, 50, and 40 mm Hg. In six dogs the cerebral metabolic rate of oxygen was determined, and the EEG was evaluated using compressed spectral analysis. Brain tissue metabolites were calculated in the other six dogs. During normotension, hypocapnia caused no deterioration of cerebral metabolism or of the EEG. Hypocapnia combined with NTG-induced hypotension caused a decrease of the power of the alpha and beta 2 spectra of the EEG at MABP's of 60 mm Hg or less. At an MABP of 40 mm Hg, brain tissue phosphocreatine and the cerebral energy charge decreased, while the brain tissue lactate:pyruvate ratio increased. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites returned to initial values, but the power of the EEG alpha and beta 2 spectra was decreased compared to baseline values. The cerebral metabolic disturbances and EEG alterations seen here with hypocapnia plus NTG-induced hypotension were similar to those previously reported with hypocapnia plus sodium nitroprusside-induced hypotension, and less than those previously reported with hypocapnia plus trimethaphan-induced hypotension. For hyperventilated patients, administration of NTG may be a better hypotensive treatment than trimethaphan, but similar in effect to sodium nitroprusside.

Animals↗

Mechanisms of synergism between arteriolar embolization and hyperthermia in a rabbit V-2 model of solitary hepatic metastasis.

In a V-2 model of solitary hepatic metastasis, residual tumor was histologically identified in the treatment field in only three of 14 (21%) animals subjected to microsphere embolization of tumor arterioles plus focal (43 degrees C, 40 min) hyperthermia compared with seven of ten (70%) subjected to focal (43 degrees C, 40 min) hyperthermia alone (P less than or equal to 0.05), five of seven (71%) (P less than or equal to 0.05) treated by occlusion plus sham heating, and five of five (100%) (P less than or equal to 0.01) sham-treated controls. Prior occlusion tended to reduce the radiofrequency power required for heat up and steady-state temperature maintenance of tumors (P less than or equal to 0.09 and P less than or equal to 0.06, respectively) and reduced the cooling rate after heating compared to unoccluded tumors (P less than or equal to 0.02) but did not affect mean time to temperature, maximum and minimum temperature measured at the tumor-normal tissue interface, and animal core temperature compared with that of the hyperthermia alone treatment group. In ten other animals with hepatic V-2 tumors of comparable size subjected to focal hyperthermia plus or minus arteriolar embolization, temperatures were continuously monitored at four additional intratumor sites in a fixed geometric orientation around the heating probe. No significant differences were noted in maximum and minimum temperatures in comparably oriented probes over a 40-min heating period between the hyperthermia and the occlusion-hyperthermia treatment groups. In five other animals with solitary V-2 hepatic implants, comparable microembolization plus or minus focal tumor heating to 43 degrees C, 40 min, did not significantly reduce tumor interstitial pH compared with pretreatment values. This study reproduces previously observed synergism between arteriolar embolization and hyperthermia but suggests the mechanism may be unrelated to observable differences in intratumor pH and thermal profile and may result from other mechanisms, perhaps by mimicking the angioocclusive effects of hyperthermia itself.

Animals↗

Distribution of radiolabeled multilamellar liposomes injected intralymphatically and subcutaneously.

The distribution of negatively charged multilamellar vesicles (MLV) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol administered subcutaneously (s.c.) and intralymphatically (i.l.) was studied in rats and dogs. In rats, the drainage of 99mTc-MLV from the s.c. space was slow, with 35% of the activity still remaining at the site of injection after 48 h and minimal systemic distribution (less than 5% at any time point). In the dog, 99mTc-MLV and 111In-MLV injected s.c. on the dorsal surface of a hindpaw were drained both by the lymphatic system and the systemic circulation; at 24 and 72 h, significant activity still remained at the site of injection. Lymphatic uptake was almost limited to the popliteal nodes and was enhanced by dividing the dose in several s.c. injections. Liver and kidney uptake was also observed, most likely as a result of direct liposome absorption into the systemic circulation. The i.l. administration (via left hindpaw) of 99mTc-MLV to a dog resulted in an immediate uptake in the abdominal and mediastinal lymph nodes, and in the liver and spleen. Compared with small unilamellar vesicles, MLV injected s.c. can provide a slower and more prolonged delivery of drugs to the regional lymph nodes.

Animals↗

Direct ovarian effect of clomiphene citrate in the rabbit.

The effects of clomiphene citrate (CC) on ovulation and ovum maturation were studied using the isolated perfused rabbit ovary. CC (10(-5) M) added to the perfusate with human chorionic gonadotropin (50 IU) did not affect ovulatory efficiency, ovulation time, oocyte maturation, or degeneration of ovulated ova and follicular oocytes. During perfusion without human chorionic gonadotropin, the percentage of follicular oocytes with germinal vesicle breakdown was significantly increased in response to CC (10(-5) M or 10(-7) M); a greater percentage of follicular oocytes was degenerated. Estradiol (100 ng/ml) added to the perfusate reversed the effect of CC on degeneration of follicular oocytes. Of follicular oocytes from ovaries perfused with CC, 79.3% were degenerated; in contrast, 25% were degenerated in ovaries treated with CC plus estradiol. These data suggest that CC has a direct ovarian effect and that ovum degeneration associated with CC may be related to an antiestrogenic action.

Animals↗

Selective occlusion and focal hyperthermia therapy of V-2 tumors in the rabbit hindlimb.

Utilizing technology recently developed in our laboratory, hypervascular, heat-resistant V-2 tumors growing in the rabbit hindlimb were variously subjected to selective vascular occlusion by embolization with Dextran M microspheres and focal hyperthermia to minimum intratumor temperatures of 43 degrees C X 40 minutes (OH), focal 43 degrees C X 40 minutes hyperthermia alone (H), selective occlusion plus sham hyperthermia (O), and sham treatment. Regional toxicity observed consisted of skin burns and muscle fibrosis in the H and OH groups and peripheral embolization in the O alone group. Tumors subjected to a single OH treatment had significantly reduced growth rate over a 28-day period of observation compared with all other treatment groups and sham-treated controls (P less than or equal to .05). Our findings suggest that the combination of selective vascular embolization and focused hyperthermia may be useful in therapy of hypervascular, heat-resistant human tumors in anatomic locations where selective occlusion and relatively intense focal heating can be performed. The regional toxicity encountered in this model reemphasizes the need for extensive thermal mapping over the heated region.

Animals↗

Supraclinoid intracarotid chemotherapy using a flow-directed soft-tipped catheter.

In an attempt to avoid toxic reactions of the eye as a complication of internal carotid arterial infusion of cisplatin, carmustine, or a combination of both for the treatment of brain tumors, a new Gore-Tex/Teflon coaxial catheter system has been used for supraclinoid placement. Catheter placement was successful in 14 of 16 attempts in eight patients. Two patients experienced eye pain and conjunctivitis--a result of the chemotherapeutic agent leaking through the Gore-Tex portion of the catheter at the infusion rate of 170 ml/h. No complications were noted as long as the infusion rate was maintained at 125 ml/h or lower.

Adult↗

Comparative effects of tamoxifen and bromocriptine on prolactin and pituitary weight in estradiol-treated male rats.

Male ACI rats were treated with estradiol to induce hyperprolactinemia and pituitary hypertrophy and hyperplasia. Animals received estradiol alone or with tamoxifen or bromocriptine for 4, 8, or 12 weeks. Estradiol treatment resulted in time-dependent increases in pituitary wet weight and serum prolactin concentrations. Tamoxifen completely blocked the increase in both variables; bromocriptine decreased but did not prevent time-dependent increases. Animals were also treated for 8 weeks with estradiol alone, followed by 4 weeks with estradiol and tamoxifen or bromocriptine. Neither compound reversed the hyperprolactinemia, although the pituitary wet weight of animals treated with bromocriptine was slightly but significantly reduced. These findings suggest that in this model if treatment is initiated simultaneously with estrogen stimulation, tamoxifen is more effective than bromocriptine at the doses studied; and, if therapy is initiated subsequent to the establishment of estrogen-induced hyperprolactinemia and pituitary hyperplasia, bromocriptine is more effective than tamoxifen at the doses studied.

Animals↗