Blowing in the wind.
Faced with healthcare demands that outstrip budgets, how do HAs prioritise services? Ray Robinson suggests four major inputs all purchasers should take into account.
Cost-Benefit Analysis↗
Biomedical subjects
R Robinson
Publications and source records attributed to R Robinson.
Moving ahead--community care in Gwent.
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Aged↗
Familial ovarian cancer.
Familial cancer clusters provide a unique opportunity to elucidate the molecular mechanisms central to the development of malignancy. We have identified four families in which 11 members developed epithelial ovarian cancer. The clinical course of disease in these individuals with familial ovarian cancer appears to be very different from that of patients with nonfamilial ovarian cancer. In order to compare these disease states, 34 cases matched for age at diagnosis (57 years), tumor histology (all adenocarcinomas), and a preponderance of advanced grade and FIGO stage of disease were selected. Patients with familial ovarian cancer exhibited a 67% 5-year survival in comparison with a 17% 5-year survival in the nonfamilial ovarian cancer cases. Preliminary studies indicate a lack of overexpression of the HER-2/neu oncogene in the familial cancer members' tumors. This may correlate with the indolent character of their disease. Abnormal p53 tumor suppressor gene expression was noted in four of six cancers tested. We also found germ line p53 mutations in three of the four families, but neither the germ line or tumor p53 prevalence was 100%. This is the first report of germ line p53 mutations associated with familial ovarian cancer and indicates that this gene may play a role in the development of some familial ovarian cancers.
Adenocarcinoma↗
The treatment of epiphora with balloon dacryocystoplasty.
We examine a new treatment for epiphora: balloon dilatation of the nasolacrimal duct, or dacryocystoplasty. The procedure, which was performed as an out-patient procedure under local anaesthetic, was carried out on 20 patients with epiphora, 17 due to anatomical and 3 due to functional obstruction. There was an overall success rate of 60%, with complete relief of symptoms in 4 patients and a symptomatic improvement in another 8 (follow-up 2-9 months, mean 4.2 months). All patients tolerated the procedure well with minimal per-operative and post-operative discomfort. A higher success rate was seen in those patients with either a low anatomical or a functional obstruction. The procedure can be easily repeated and, if unsuccessful, still allows a dacryocystorhinostomy to be performed at a later date.
Adolescent↗
Systemic cell-mediated immune reactivity in women with recurrent vulvovaginal candidiasis.
It has been suggested that impaired cell-mediated immunity (CMI) against Candida antigens is responsible for susceptibility to recurrent vulvovaginal candidiasis (RVVC) in adult women. To address this, we conducted a comprehensive longitudinal study examining in vivo and in vitro systemic CMI reactivity in RVVC patients. Results showed that RVVC patients frequently demonstrated a transient loss of Candida-specific delayed cutaneous skin test reactivity during episodes of symptomatic vaginitis. In contrast, in vitro peripheral blood lymphoproliferation and Th1-type lymphokine production by RVVC patients in response to a T cell mitogen and multiple Candida and bacterial antigens were similar to controls both during acute episodes of vaginitis and during periods of infection-free remission. These results suggest that women with RVVC have no detectable impairment of systemic CMI in peripheral blood and that transient reductions in skin test reactivity appear to be a result of vaginal Candida infection and not a predisposing factor to RVVC.
Adolescent↗
Safety belt restraints and compartment intrusions in frontal and lateral motor vehicle crashes: mechanisms of injuries, complications, and acute care costs.
A 3-year prospective study examined 76 frontal (F) and 45 lateral (L) motor vehicle crash (MVC) patients with regard to seatbelt restraint use and occupant compartment contact and intrusion injuries. These 121 MVC victims with multiple injuries (39 belted [B] and 82 non-belted [NB]), admitted to a level I trauma center, were studied by accident reconstruction and medical data analysis. They had a MVC mean impact velocity (delta V) of 30 +/- 11 mph and an injury Severity Score of 29 +/- 12. Proper restraint use reduced brain injury in F MVCs (30% FB vs. 47% FNB) but had no effect in L MVCs (63% LB vs. 30% FB [p < 0.06]). Belt use did not protect against lung, liver, spleen, pelvis, or lower extremity (LE) injury. These appeared to be more a function of crash direction, with LE injuries higher in F crashes (p < 0.04) and pelvis injuries (p < 0.001) higher in L crashes. In FB crashes, however, properly used safety restraints were the primary cause of bowel or colon injuries (p < 0.006). Belts did not prevent thoracic or abdominal solid organ injuries in L crashes. Contact-intrusions (CI) of the car occupant compartment in F crashes were the main cause of brain (A-pillar), lung and liver (steering wheel and instrument panel), and LE (toepan) injuries; but in L crashes, side-door CI caused lung, aorta, liver, and pelvic injuries. In contrast, contact-only (CO) injuries of the steering assembly were mainly responsible for injuries to the lung, heart, and liver in F crashes, and side-door CO for lung, liver, and spleen injuries in L crashes. Deaths and complications after injury were higher among F MVC occupants, or when delta V was > or = 30 mph. Hospital and professional costs reflect the complex care needed for victims of multiple injuries: FB, $99,000; FNB, $95,000; LB, $75,000; LNB, $79,000; total, $10.7 million. Present vehicle safety standards are not adequate, and structural design changes are needed to improve restraints and protect occupants from intrusion-related injuries.
Abdominal Injuries↗
Microwave sterilization of polyethylene catheters for intermittent self-catheterization.
A standard household 650 W microwave oven was used to sterilize polyethylene catheters of the type used for intermittent self-catheterization. The catheters were infected with Proteus sp. bacteria and microwaved at 650 W for periods of 2, 4, 6 and 8 minutes. The effect of microwaving was assessed by determining the resultant colony counts following catheter culture. It was determined that 6 minutes of microwaving were required to achieve sterility. It is suggested that use of a microwave oven is a reliable and cost-effective method of sterilizing polyethylene catheters for intermittent self-catheterization.
Catheterization↗
Persistent mild hip deformation in preterm infants.
Preterm infants often develop a postural deformation of the legs with wide hip abduction and external rotation giving a 'frog leg' posture. It has been shown that the deformation persists at the age of 3-4.5 years and the use of postural techniques aimed at reducing the deformation is recommended.
Child, Preschool↗
Follow-up study on premature infants with and without retinopathy of prematurity.
The ocular complications in population of 131 premature infants, with and without retinopathy of prematurity (ROP) are reported. An increased incidence of strabismus (20% with ROP and 25% without ROP) and myopia (27.5% with ROP and 8.8% without ROP) was shown. Significant visual loss occurred in 10.7% overall, increasing to 35% with stage 3 disease and 100% with stage 4. With the increased survival rate of premature infants, the relevance to future management of this expanding group of young people is considered.
Birth Weight↗
H-ras-1 point mutations in soft tissue sarcomas.
The H-ras-1 protooncogene is activated by single base substitutions occurring in either codon 12, 13, or 61. These mutations have been described with varying frequencies in several human tumor types. Since ras oncogenes were first discovered as the transforming sequences of Harvey and Kirsten murine sarcoma viruses (which also contain activating point mutations compared to the homologous cellular sequences), we wished to investigate the possibility that ras mutations might also occur in human sarcomas. We extracted DNA from six malignant fibrous histiocytomas (MFH), three embryonal rhabdomyosarcomas (ER), one alveolar rhabdomyosarcoma, one pleomorphic rhabdomyosarcoma, and one leiomyosarcoma. The DNA from regions flanking codons 12/13 and codon 61 was amplified by the polymerase chain reaction and sequenced with an automated DNA sequencer. As controls, we amplified and sequenced normal DNA (placenta) and DNA with known point mutations (T24 bladder carcinoma cells). We found three cases with mutations, all occurring in codon 12. One ER showed a G-to-T mutation in the second position of codon 12 (coding for valine instead of glycine). Two MFHs showed G-to-A mutations in the second position of codon 12 (coding for aspartic acid instead of glycine). Although a limited number of cases were sampled, we conclude that study of H-ras-1 mutations may be relevant to MFH and ER. Additional studies of N and K-ras mutations as well as more cases investigating H-ras will be required before we can ascertain the significance of ras mutations in the oncogenesis of human soft tissue sarcomas.
Base Sequence↗
Health economics and economists in the NHS.
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Cost-Benefit Analysis↗
'Spasticity' in the Devon rex cat.
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Animals↗
Aldolase-DNA interactions in a SEWA cell system.
In this report we demonstrate the novel finding that aldolase A interacts with DNA sequences in mouse SEWA sarcoma cells. This interaction was initially observed through the identification of a 40 kDa protein which was eluted from a DNA affinity chromatography column consisting of the long terminal repeat (LTR) of the endogenous intracisternal A-type particle (IAP). Microsequencing analysis identified this 40 kDa protein as the glycolytic enzyme, aldolase A. The use of specific anti-aldolase antibodies enabled the identification and subsequent purification of aldolase from the nuclear protein fraction of two SEWA sublines, one that is adherent and one that grows in suspension. In order to confirm our initial finding that aldolase is capable of interacting with DNA, proteins from each subline were immunopurified with anti-aldolase antibodies, eluted and then tested for their ability to interact with IAP-LTR DNA sequences. Interestingly, only aldolase derived from the anchorage dependent SEWA cells was capable of interacting with the IAP-LTR, however, several cell lines derived from human tumors also exhibited this activity. Subsequent studies revealed the ability of aldolase to interact with some but not every DNA sequence tested, implying that there may be a minimal DNA conformation and/or sequence requirement for this activity. The presence of aldolase A in the nuclei and its ability to interact with certain DNA sequences suggest a novel role for this metabolic enzyme.
Animals↗
Interaction of SEWA sarcoma cell proteins with the intracisternal A-type particle long terminal repeat DNA sequence.
Intracisternal A-type particle (IAP) transcripts are endogenous retrovirus-like sequences expressed during specific stages of normal development and in a variety of murine tumors. In this study, we have analyzed two cell lines derived originally from the SEWA murine osteosarcoma and grown either as ascites or as solid tumors, for proteins that might regulate IAP expression. We found that subline AA7-NA, originally derived from the ascites tumor, expressed about five times more IAP RNA than the AS12-AD subline, which was derived from a solid tumor. In view of this finding, we examined the binding of cellular proteins from the two cell lines to the 5' end of an IAP long terminal repeat sequence. Gel retardation assays of DNA-protein complexes and DNase I footprinting assays identified several DNA sequences within the long terminal repeat fragment that were protected by protein extracts from both SEWA sublines. Gel retardation assays using specific synthetic oligonucleotide sequences that correspond to two of these protected regions revealed different patterns of DNA-protein complexes with extracts from the two SEWA sublines. These data suggest that expression of IAP sequences is regulated by complex mechanisms involving several proteins that appear to differ between the two sublines.
Animals↗
Evidence that oocyte maturation induced by an oncogenic ras-p21 protein and insulin is mediated by overlapping yet distinct mechanisms.
We have recently shown that a peptide (residues 35-47) from a functional region of the ras p21 protein, thought to be involved in the binding of p21 to GTPase activating protein, the antibiotic azatyrosine, known to induce the ras-recision gene, and the selective protein kinase C inhibitor, CGP 41,251, all inhibit oncogenic p21 protein-induced maturation of oocytes in a dose-dependent manner. We now show that these three agents only partially inhibit insulin-induced oocyte maturation, known to be dependent on activation of cellular p21 protein. On the other hand, the anti-p21 protein antibody Y13-259 completely inhibits both insulin- and oncogenic p21 protein-induced maturation as does a tetrapeptide, CVIM, known to block the enzyme farnesyl transferase which covalently attaches the farnesyl moiety to the p21 protein allowing it to attach to the cell membrane. Our results suggest that while the oncogenic and insulin-activated normal p21 proteins share certain elements of their signal transduction pathways in common, these pathways diverge and allow for selective inhibition of the oncogenic pathway.
Alanine↗