Laparoscopic versus open mesh repair of inguinal hernia. Recurrence rate is true test of hernia repair.
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Hernia, Inguinal↗
Biomedical subjects
K Rose
Publications and source records attributed to K Rose.
Management of day-surgery patients with cataract attending a peripheral ophthalmic clinic.
PURPOSE: To compare two organisational models of management for patients with cataract referred to a peripheral ophthalmic clinic who underwent day-surgery at a main eye hospital. METHOD: Patients were randomised into two groups. The experimental group (n = 25) received pre-operative assessment by a trained ophthalmic nurse at the peripheral clinic immediately following diagnosis of cataract and diary-booking for surgery. The control group (n = 24) received a separate appointment for pre-operative assessment at the main hospital. For all patients, the first review appointment (3 or 5 days post-operatively) and all subsequent review was at the peripheral clinic. Outcome measures included: visual acuity, subjective visual function (VF-14), anxiety and depression (HADS), semi-structured interviews to ascertain patient satisfaction, and a cost-benefit analysis. RESULTS: There were no significant differences at any time between the experimental and control groups with respect to visual acuity, subjective visual function or anxiety and depression. The experimental model was found to be more cost-effective and provided a less fragmented means of care delivery. The majority of patients in both groups expressed satisfaction with their care but, overall, the experimental model was preferred. CONCLUSIONS: Nurse-led pre-operative assessment of patients with cataract at a peripheral ophthalmic clinic is safe, cost-effective and is preferred by patients.
Aged↗
Planning and managing research into day-surgery for cataract.
Between 1995 and 1997, a randomized controlled study, funded by the Department of Health, was carried out into the management of patients with cataract attending a peripheral ophthalmic clinic and who had been assessed as suitable for day-surgery. The research took place in a clinical setting and it was accepted from the outset that, while such studies have the power to give information about the real clinical world, this also means that the research is potentially at the mercy of events within that world. The purpose of this paper is to report how the study was set up and integrated into the clinic. First, a literature review was undertaken in order to focus the aims of the study more clearly. Second, drawing on principles of action research, clinical and research staff worked together to implement the study. This strategy allowed a flexible approach to the research which enabled problems to be handled as they arose.
Ambulatory Surgical Procedures↗
Building relationships with discharge planners.
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Community Health Nursing↗
Tension-free mesh hernia repair: recovery and recurrence after one year.
The outcome of 200 consecutive patients with inguinal hernias repaired by the tension-free mesh technique at a specialist clinic was assessed one year after operation. There were no recurrences and no major complications. The wound infection rate was 1%. Less than 10% of patients had only minor complaints and 99% of patients were satisfied or very satisfied with the operation and its outcome. Low recurrence rates after one year imply low long-term recurrence and testify to the benefits of a specialist approach.
Adolescent↗
Short-term insulin-induced glycogen formation in primary hepatocytes as a screening bioassay for insulin action.
We describe a novel bioassay to measure specific insulin-like activity in primary cultures of rat hepatocytes by determination of [3H]glycogen from d-[6-3H]glucose. The dose-response curve of insulin in this assay exhibited an EC50 of 0.42 (+/-0.04) nM, which is comparable to the dissociation constant of insulin from its receptor in hepatocytes. We used this assay to examine possible residual insulin-like activity of the four major fragments formed upon insulin degradation by insulin protease. Fragments A1-13B1-9, A1-14B1-9,and A14-21B14-30 showed no measurable activity. Although preparations of fragment A14-21B10-30 displayed dose-dependent agonist activity with an EC50 of 380 (+/-40) nM, we conclude that this was due to an insulin-like impurity since the chemically synthesized fragment showed no such activity. In summary, this bioassay demonstrates the action of insulin on glycogen formation in hepatocytes and provides a rapid and sensitive measurement of insulin-like activity which could facilitate screening studies.
Animals↗
Fastrach--a new intubating laryngeal mask airway: successful use in patients with difficult airways.
PURPOSE: The Laryngeal Mask Airway-Fastrach (Fastrach) is a new modified laryngeal mask with the capability for guided tracheal intubation while maintaining ventilation. We report the use of this device in patients with proven difficult airways, following induction of general anaesthesia. CLINICAL FEATURES: After induction of general anaesthesia, having failed tracheal intubation with conventional laryngoscopy, the first patient's trachea was intubated via the Fastrach with fibreoptic guidance. In the second and third patients, who had documented histories of difficult tracheal intubation, tracheal intubation was performed electively with the Fastrach following induction of inhalational anaesthesia with spontaneous respiration. CONCLUSION: The Fastrach is an option in the management of the airway following failed tracheal intubation or for elective tracheal intubation in patients with anatomically difficult airways.
Aged↗
Plasmodium falciparum polyoximes: highly immunogenic synthetic vaccines constructed by chemoselective ligation of repeat B-cell epitopes and a universal T-cell epitope of CS protein.
Effective immunoprophylaxis directed against the pre-erythrocytic stages of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic background. In order for a synthetic peptide malaria vaccine to meet these requirements, problems associated with genetic restriction, peptide chemistry, adjuvant formulation and physiochemical characterization of the final synthetic vaccine product must first be overcome. To address these issues, five polyoxime vaccine candidates have been constructed by ligating purified peptide epitopes of the P. falciparum CS protein to a branched template via oxime bonds. All five constructs, including two based on templates containing the synthetic adjuvant tripalmitoyl-S-glyceryl cysteine (Pam3Cys), were of sufficient purity for characterization by mass spectrometry. The immunogenicity of the malaria polyoximes in different murine strains was compared to that of multiple antigen peptide (MAP) constructs synthesized by standard step-wise synthesis. A tri-epitope polyoxime-Pam3Cys construct, based on the repeats and a universal T-cell epitope that contains both helper and CTL epitopes of the CS protein, was shown to be a precisely-defined synthetic malaria vaccine candidate that was highly immunogenic in murine strains of diverse H-2 haplotypes.
Adjuvants, Immunologic↗
Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.
To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.
Animals↗
Yeast meiotic mutants proficient for the induction of ectopic recombination.
A screen was designed to identify Saccharomyces cerevisiae mutants that were defective in meiosis yet proficient for meiotic ectopic recombination in the return-to-growth protocol. Seven mutants alleles were isolated; two are important for chromosome synapsis (RED1, MEK1) and five function independently of recombination (SPO14, GSG1, SPOT8/MUM2, 3, 4). Similar to the spoT8-1 mutant, mum2 deletion strains do not undergo premeiotic DNA synthesis, arrest prior to the first meiotic division and fail to sporulate. Surprisingly, although DNA replication does not occur, mum2 mutants are induced for high levels of ectopic recombination. gsg1 diploids are reduced in their ability to complete premeiotic DNA synthesis and the meiotic divisions, and a small percentage of cells produce spores. mum3 mutants sporulate poorly and the spores produced are inviable. Finally, mum4-1 mutants produce inviable spores. The meiotic/sporulation defects of gsg1, mum2, and mum3 are not relieved by spo11 or spo13 mutations, indicating that the mutant defects are not dependent on the initiation of recombination or completion of both meiotic divisions. In contrast, the spore inviability of the mum4-1 mutant is rescued by the spo13 mutation. The mum4-1 spo13 mutant undergoes a single, predominantly equational division, suggesting that MUM4 functions at or prior to the first meiotic division. Although recombination is variably affected in the gsg1 and mum mutants, we hypothesize that these mutants define genes important for aspects of meiosis not directly related to recombination.
Alleles↗
Calcium- and hydroxyapatite-binding properties of glucuronic acid-rich and iduronic acid-rich glycosaminoglycans and proteoglycans.
This study describes the interaction of a small chondroitin sulphate proteoglycan and the glycosaminoglycans chondroitin 4-sulphate, dermatan sulphate and heparan sulphate with hydroxyapatite. All macromolecules possessed a high affinity, with the iduronic acid-rich dermatan sulphate and heparan sulphate displaying higher adsorption maxima than the glucuronic acid-rich chondroitin 4-sulphate. At similar concentrations, dermatan sulphate produced a 30% inhibition of hydroxyapatite-induced crystal growth, whilst chondroitin 4-sulphate yielded 50% inhibition. Estimation of the calcium binding capacity of these glycosaminoglycans using equilibrium dialysis indicated that chondroitin 4-sulphate bound five times more calcium than dermatan sulphate at a calcium concentration similar to that of serum. The data indicate a possible important role for chondroitin 4-sulphate in dentinogenesis where it is the dominant glycosaminoglycan, since it could act as a capture point for calcium ions during mineralisation, with the leucine-rich domain of its parent proteoglycan acting as anchor points to type I collagen.
Adsorption↗
In vitro evidence that rabbit distal colonic muscularis mucosae has a Clostridium difficile toxin A receptor.
In the rabbit ileum Clostridium difficile toxin A causes inflammation and mucosal damage via a specific glycoprotein receptor that contains alpha-D-galactose. In rabbit colon toxin A also causes inflammation, and this is associated with increased myoelectric activity and eicosanoid production. The present in vitro study was undertaken to determine if a toxin A receptor on one or more layers of colonic smooth muscle could mediate the motor effects of this agent. Toxin A (20-100 microg/ml) was without effect on longitudinal and circular muscle but had two different effects on the muscularis mucosae. Initial exposure to the toxin caused increased numbers of spontaneous contractions and a small, atropine-, tetrodotoxin-, and indomethacin-resistant increase in resting tone. More importantly, however, 30-min exposure to toxin A resulted in attenuated muscularis mucosae responses to acetylcholine and K+. Both the small excitatory and the larger inhibitory effects of toxin A were abolished by pretreatment with the lectin BS-1, which binds to toxin A receptors, but not by the nonreceptor-binding lectin DBA. These data strongly suggest that toxin A causes significant motor effects on the distal colonic muscularis mucosae via a receptor-mediated mechanism. These mechanical data were supported by the presence of histologically demonstrable toxin A and BS-1 binding sites on the muscularis mucosae but not on either the longitudinal or circular muscle layers, both of which were unresponsive to the toxin. By depressing muscularis mucosae function and, ultimately, mucosal movement as a result of toxin A production, C. difficile may promote its own proliferation, thus further contributing to the development of antibiotic-associated colitis.
Acetylcholine↗
Phase I and pharmacokinetic trial of aminopterin in patients with refractory malignancies.
PURPOSE: Aminopterin (AMT) is a potent folate analog that is no longer in routine clinical use. Because of laboratory data that suggests improved metabolism of AMT versus methotrexate (MTX) in lymphoblasts, we developed a phase I trial to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic profile of AMT. PATIENTS AND METHODS: Twenty patients with refractory malignancies were treated. The starting dose of AMT was 2.5 mg/m2 every 12 hours for two doses weekly: the dose of AMT was decreased and leucovorin (LV) rescue was added after the DLT was observed. Pharmacokinetics were performed after both intravenous (i.v.) and oral AMT administration. RESULTS: Mucosal toxicity was dose-limiting and resulted in the need for a dose reduction (dose level 2: AMT 2 mg/m2 every 12 hours for two doses weekly) and, subsequently, the addition of scheduled LV rescue (dose level 3: AMT 2 mg/m2 every 12 hours for two doses followed by LV 5 mg/m2 orally every 12 hours for two doses, starting 24 hours after the second dose of AMT). The mean areas under the curve (AUC) for the i.v. (n = 14) and oral (n = 13) doses were 1.20 +/- 0.09 (SE) and 1.05 +/- 0.14 micromol x h/L respectively. The half-life was 3.64 +/- 0.28 hours and the oral bioavailability in 12 matched subjects was 83.5% +/- 8.3%. One patient with endometrial adenocarcinoma achieved a complete response (CR) and remains on therapy at 11+ months. Seven patients had stable disease (SD) for 8 weeks or greater, which included one patient with a metastatic nerve sheath tumor who was stable for 9 months. CONCLUSION: We conclude that AMT has good oral bioavailability and that, when given on a q12 hour x two weekly schedule, the MTD is 2 mg/m2 with delayed LV rescue.
Administration, Oral↗
Differential regulation of individual sulfotransferase isoforms by phenobarbital in male rat liver.
Xenobiotics that induce the cytochromes P450 also produce changes in rat hepatic sulfotransferase (SULT) gene expression. In the present study, male Sprague-Dawley rats were treated for 3 consecutive days with doses of phenobarbital (PB) that induce cytochrome P450 2B1/2 expression. The effects of PB treatment on hepatic aryl SULT (SULT1) and hydroxysteroid SULT (SULT2) mRNA and immunoreactive protein levels and on mRNA expression of individual SULT1 and SULT2 enzyme isoforms were characterized. PB suppressed SULT1A1 mRNA levels, increased the expression of the SULT-Dopa/tyrosine isoform, and did not produce significant changes in SULT1C1 and SULT1E2 mRNA expression. In rats injected with the highest test dose of PB (100 mg/kg), hepatic SULT1A1 mRNA levels were decreased to approximately 42% of control levels and SULT-Dopa/tyrosine mRNA levels were increased to approximately 417% of vehicle-treated control levels. Like the SULT1 subfamily, individual members of the SULT2 gene subfamily were differentially affected by PB treatment. PB (35, 80, and 100 mg/kg) suppressed SULT20/21 mRNA expression to approximately 61, approximately 30, and approximately 41% of vehicle-treated control levels, respectively. In contrast, SULT60 mRNA levels were increased to approximately 162% of control levels and SULT40/41 mRNA levels were increased to approximately 416% of vehicle-treated control levels in rats treated with 100 mg/kg PB. These studies support a complex role for PB-mediated effects on the SULT multigene family in rat liver. Because individual SULT1 and SULT2 enzyme isoforms are known to metabolize a variety of potentially toxic substrates, varied responses to PB among members of the SULT multigene family might have important implications for xenobiotic hepatotoxicity.
Animals↗
Primary and secondary care partnership.
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Cataract↗
Development of an isotope dilution assay for precise determination of insulin, C-peptide, and proinsulin levels in non-diabetic and type II diabetic individuals with comparison to immunoassay.
We describe the application of a stable isotope dilution assay (IDA) to determine precise insulin, C-peptide, and proinsulin levels in blood by extraction from serum and quantitation by mass spectrometry using analogues of each target protein labeled with stable isotopes. Insulin and C-peptide levels were also determined by immunoassay, which gave consistently higher results than by IDA, the relative difference being larger at low concentrations. Insulin, C-peptide, and proinsulin levels were all shown by IDA to be higher in type II diabetics than in non-diabetics, with mean values rising from 22 (+/- 2) to 92 (+/- 8), 335 (+/- 11) to 821 (+/- 24), and 6 (+/- 1) to 37 (+/- 3) pM, respectively. Interestingly, the ratio between IDA and immunoassay values for insulin levels increased from 1.3 in non-diabetics to 1.7 in type II diabetics. The ratio between proinsulin and insulin levels by IDA increased from 0.24 in non-diabetics to 0.36 in type II diabetics, whereas the ratio between C-peptide and insulin levels by IDA decreased from 17.6 to 10.7. This disproportionate change in protein levels between different types of individuals has implications for the metabolism of insulin in the diabetics studied (type II) and suggests that C-peptide levels are not always a reliable guide as to pancreatic insulin secretion. In addition, levels of the 33-residue C-peptide (partially trimmed form) were shown to be less than 10% that of the fully trimmed 31-residue C-peptide levels, and we tested IDA in a clinical context by two post-pancreatic graft studies. IDA was shown to give direct, positive identification of the target protein with unrivaled accuracy, avoiding many of the problems associated with present methodology for protein determination.
C-Peptide↗
How informal carers cope with terminal cancer.
This article reports selected findings from a qualitative study of informal carers. The study focused on people caring for relatives with terminal cancer and the findings reported here reflect how they cope with their relative's pain and medication. The author recommends that nurses involve carers in the decision making process to alleviate the stress carers experience and utilise their specialist knowledge of the patient.
Adaptation, Psychological↗
Differential responses in anterior pituitary luteinizing hormone (LH) content and LH beta- and alpha-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin.
Anterior pituitary gland contents of LH and LH beta- and alpha-subunit mRNAs, and circulating concentrations of LH and testosterone, were determined in bulls treated with the LH-releasing hormone (LHRH) agonist deslorelin. Brahman (Bos indicus) bulls (14-month-old) were allocated to two groups and received the following: Control (n = 5), no treatment; Deslorelin (n = 4), four deslorelin implants (approximately 200 micrograms total deslorelin/day) for 36 d. Plasma concentrations of LH were higher in bulls treated with deslorelin on Day 1, had returned to typical levels by Day 8, and did not differ for control bulls and bulls treated with deslorelin from Day 8 to Day 29. Pituitary content of LH on Day 36 was reduced (P < 0.001) in bulls treated with deslorelin (33 +/- 4 ng/mg) compared with control bulls (553 +/- 142 ng/mg). Relative pituitary content of LH beta-subunit mRNA was also reduced on Day 36 in bulls treated with deslorelin (Control, 0.65 +/- 0.10; Deslorelin, 0.22 +/- 0.04; P = 0.003). However, alpha-subunit mRNA relative content did not differ (Control, 0.73 +/- 0.15; Deslorelin, 1.06 +/- 0.12; P > 0.05). Plasma concentrations of testosterone were increased over the period of the experiment in the bulls treated with deslorelin compared with control bulls. This is the first demonstration of reduced pituitary content of LH beta-subunit mRNA and LH, and unaltered content of alpha-subunit mRNA, in bulls treated with LHRH agonist. This was associated with apparently typical plasma concentrations of LH and elevated plasma testosterone. The anterior pituitary in bulls treated with LHRH agonist, therefore, undergoes classical desensitization and downregulation, but plasma LH and testosterone are not suppressed.
Animals↗