PubMed Health⌕ Search

Biomedical subjects

R C King

Publications and source records attributed to R C King.

At least 19 recordsLinked to original sources
PubMed1997

Nurse cell polytene chromosomes of Drosophila melanogaster otu mutants: morphological changes accompanying interallelic complementation and position effect variegation.

Combinations of certain mutant alleles of the ovarian tumor gene permit the production of viable eggs. Two alleles that behave in this way are otu7 and otu11. Females homozygous for either allele are sterile, and their ovarian nurse cells (NC) contain giant polytene chromosomes of various morphologies. Fertile flies (otu+/otu+, otu+/otu7, otu+/otu11) have endopolyploid nurse cells with typical dispersed chromosomes. Fertile hybrids (otu7/otu11) produce large numbers of polytene chromosomes comparable to, and often larger than, classic salivary gland (SG) chromosomes. Therefore, these otu hybrids provide a unique system for studying, at the chromosomal level, the activation and expression of genes functioning during oogenesis. The otu gene encodes a long and a short isoform. The normal long isoform appears to be responsible for the dispersion of chromosomes during the endomitolic DNA replications occurring in ovarian NCs. The genetic inactivation of euchromatic genes placed next to pericentric heterochromatin by a chromosomal rearrangement is accompanied by the compaction of corresponding chromosome regions. A comparative study of the manifestation of position-effect variegation for the polytene chromosomes of SG cells and NCs was made using the Dp(1;1)pn 2b and Dp(1;f)1337 rearrangements. The percentage frequencies of block formation in the SG and NC nuclei for Dp(1;1)pn 2b rearrangement were 92.6% vs. 15.8%, respectively; for Dp(1;f) 1337, these values were 56.8% vs. 9.7%. Therefore heterochromatin belonging to germ line chromosomes is in a configuration that is far less likely to inactivate inserted segments of euchromatin than is heterochromatin from somatic chromosomes.

Alleles↗
PubMed1997

Intravenous phenylephrine preconditioning of cardiac grafts from non-heart-beating donors.

BACKGROUND: Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heartbeating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning. METHODS: Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 microg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia. RESULTS: Phenylephrine 25 microg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 +/- 0.5 versus 7.7 +/- 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 +/- 5.3 versus 41.0 +/- 3.4 mm Hg; p = 0.04). Phenylephrine 25 microg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09). CONCLUSIONS: Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.

Analysis of Variance↗
PubMed1997

Low-dose sodium nitroprusside reduces pulmonary reperfusion injury.

BACKGROUND: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension. METHODS: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion. RESULTS: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs. CONCLUSIONS: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.

Animals↗
PubMed1996

Non-heart-beating donors: a model of thoracic allograft injury.

4ACKGROUND. Non-heart-beating donors (NHBDs) have been proposed for the critical shortage of donors for cardiac and pulmonary transplantation. We determined the effects of prearrest hypoxia and postarrest warm ischemia on cardiac and pulmonary allografts procured from NHBDs undergoing hypoxic arrest. METHODS. Rabbit hearts and lungs were procured from separate donors and placed on isolated blood perfusion circuits. Controls were excised and perfused without ischemia. Heart from NHBDs underwent either prearrest hypoxic perfusion alone or consecutive periods of prearrest hypoxic perfusion and 20 minutes of postarrest warm ischemia. A third group of hearts underwent 30 minutes of warm, global ischemia alone. Two groups of pulmonary allografts were studied using similar hypoxic perfusion/20-minute ischemia and 30-minute ischemia donors. RESULTS. Prearrest hypoxic perfusion clearly causes significant dysfunction of cardiac allografts from NHBDs compared with nonischemic controls. Prearrest hypoxic perfusion combined with postarrest ischemia results in an additive degree of dysfunction more severe than a similar period of warm ischemia alone. Both groups of experimental lungs displayed function similar to that of nonischemic controls in terms of pulmonary hemodynamics, airway resistance, and oxygenation potential. CONCLUSIONS. We conclude that prearrest hypoxic perfusion significantly contributes to the dysfunction of NHBD cardiac allografts. Pulmonary allografts may be more amenable to procurement of NHBDs.

Animals↗
PubMed1996

Both blood and crystalloid-based extracellular solutions are superior to intracellular solutions for lung preservation.

OBJECTIVE: Lung transplantation remains limited by donor organ ischemic time, inadequate graft preservation, and reperfusion injury. We evaluated lung preservation with use of an extracellular solution, with or without the addition of blood, as compared with preservation with the intracellular Euro-Collins solution. METHODS: With use of an isolated, whole blood perfused/ventilated rabbit lung model, we studied three groups of animals. Lungs were flushed with Euro-Collins, low-potassium dextran, or 20% blood-low-potassium dextran solution. Lungs were harvested en bloc, stored inflated at 4 degrees C for 18 hours, and then reperfused at 60 ml/min with whole blood. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, and dynamic airway compliance were obtained. Fresh, nonrecirculated venous blood was used to determine the single-pass pulmonary venous-arterial oxygen gradient. RESULTS: Lungs preserved with Euro-Collins solution demonstrated elevated pulmonary artery pressure and pulmonary vascular resistance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran solutions (pulmonary artery pressure: 40.8 +/- 2.2 mm Hg vs 28.9 +/- 2.4 mm Hg and 28.3 +/- 1.5 mm Hg, respectively, p < 0.001; pulmonary vascular resistance: 46.0 +/- 3.1 x 10(3) dynes x sec x cm(-5) vs 29.0 +/- 4.2 x 10(3) dynes x sec x cm(-5) and 28.8 +/- 2.3 x 10(3) dynes x sec x cm(-5), respectively, p < 0.001). Euro-Collins solution-preserved lungs demonstrated a significant drop in compliance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran (-21.9% +/- 4.7% vs 1.8% +/- 3.3% and 1.4% +/- 6.2%, respectively; p = 0.002). Oxygenation was improved with low-potassium dextran and 20% blood-low-potassium dextran solutions as compared with that with Euro-Collins solution (296.3 +/- 54.6 mm Hg and 290.2 +/- 66.4 mm Hg, respectively, vs 37.2 +/- 4.6 mm Hg; p = 0.001). CONCLUSIONS: Extracellular solutions provided superior preservation of pulmonary function in this rabbit lung model of ischemia-reperfusion. However, the addition of blood does not confer any demonstrable advantage over low-potassium dextran solution alone with use of an 18-hour period of cold ischemia.

Animals↗
PubMed1996

Parathyroid visualization with cibacron blue/BB5-G1.

BB5-G1 is a murine monoclonal antibody with proven affinity for human parathyroid tissue. The authors conjugated BB5-G1 to cibacron blue, a water-soluble dye, in an attempt to enhance intraoperative parathyroid visualization. Athymic nude mice possessing intramuscularly implanted human parathyroid tissue were infused with the conjugate, then surgically explored. Intraoperative findings were video-captured, then analyzed by three independent observers and by computer, generating subjective and objective data quantifying parathyroid visualization. Parathyroid tissue implants were stained and were easily visualized. The implants in the test mice displayed higher computer-generated color intensity ratings (mean, 10.25 units) compared to control mice (mean, 6.10 units) (p<0.5). Histologic sections confirmed the presence of dye and antibody within parathyroid tissue. This represents the first study to use such a conjugate to selectively enhance parathyroid visualization.

Animals↗
PubMed1996

Impaired bronchial healing after lung donation from non-heart-beating donors.

BACKGROUND: Bronchial viability after lung transplantation remains a concern. Modern preservation methods, surgical technique, and limited cold ischemic periods have decreased the frequency of bronchial complications. However, lungs procured from non-heart-beating donors are subjected to a mandatory period of warm ischemia. We investigated bronchial healing in a porcine survival model of left lung transplantation using organ procurement from non-heart-beating donors after a 60-minute period of warm ischemia. METHODS: Fourteen adult domestic swine underwent left lung transplantation. All lungs were preserved with cold Euro-Collins flush and stored inflated at 4 degrees C. Control lungs (n = 5) were flushed, harvested, and stored for 2 hours before implantation. Experimental lungs (n = 9) were procured from non-heart-beating donors. These lungs were subjected to 60 minutes of warm ischemia before flush and harvest, followed by 2 hours of cold storage before implantation. After 21 days of immunosuppression with prednisone, azathioprine, and cyclosporine, pulmonary function was assessed. Bronchial viability was evaluated with bronchoscopy and, at autopsy, followed by histologic analysis. RESULTS: Implantation time did not differ significantly between the control group and the experimental group (59.6 +/- 2.1 versus 64.4 +/- 2.9 minutes, p = 0.24). Control swine exhibited no evidence of ischemic injury to the donor bronchus. In contrast, six of nine lungs procured from non-heart-beating donors showed evidence of ischemic bronchial injury (p = 0.031 versus control). Findings ranged from hypovascular edematous mucosa to necrosis and sloughing of the mucosa throughout the entire donor bronchial tree. The remaining three non-heart-beating donor lungs exhibited normal lung function and bronchial healing. CONCLUSIONS: We conclude that 60 minutes of warm ischemia for lungs procured from non-heart-beating donors results in impaired bronchial viability with current preservation techniques. Thirty minutes of warm ischemia may be the acceptable limit for lung procurement from non-heart-beating organ donors.

Animals↗
PubMed1994

Dermoid cyst in the floor of the mouth. Review of the literature and case reports.

Dermoid cyst, frequently used to describe three closely related histologic cysts, the dermoid, epidermoid, and teratoma, is commonly considered a rare finding in the floor of the mouth. This review, which identifies 195 case reports of dermoid cysts in the floor of the mouth, has unveiled some findings that do not support conclusions expressed in previous articles. Examination of the literature includes muscle influence on clinical presentation and surgical approaches, locations, age distribution, histologic distribution, infection rate, incidence of multiple cysts, fibrous attachments, airway problems, anesthesia administration, surgical difficulties, and diagnostic aids. Brief suggestions in treatment are made in light of the clinical, radiographic, and historic findings. Three clinical cases are also included.

Adolescent↗
PubMed1993

Risks and benefits of using Marlex mesh in chest wall reconstruction.

The records of 101 patients who had undergone chest wall reconstruction both with and without stabilization of the chest wall by Marlex mesh were reviewed to see if Marlex reduced ventilator dependence and hospital stay, and to determine whether the use of Marlex was associated with any increased risk of infection. In 40 patients in whom Marlex was used, the mean number of days on postoperative ventilator support was 0.8, and mean hospital stay was 9.7 days. In 61 patients in whom Marlex was not used, the mean number of days on ventilator support was 4.9, and mean hospital stay was 17.5 days. These differences were statistically significant (p = 0.03, p = 0.006). Two patients in the Marlex-stabilized group (5%) developed wound infections, but these were preceded by ischemic necrosis of overlying flaps. None of the patients without Marlex developed wound infections. That difference was not statistically significant. We conclude that the use of Marlex in chest wall reconstruction does not significantly increase the risk of wound infection, provided that overlying tissues are properly vascularized and remain viable, and that synthetic mesh does improve chest wall stability and reduce ventilator dependence and overall hospital stay.

Adult↗
PubMed1992

Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo.

OBJECTIVES: The aim was to determine whether dofetilide, a new class III antiarrhythmic agent, could reduce the heterogeneity of repolarisation produced by rapid cardiac pacing and to compare it with quinidine. Increased heterogeneity of repolarisation times may be causally linked to malignant cardiac re-entrant arrhythmias. METHODS: Studies were performed in open chest, artificially ventilated, pentobarbitone anaesthetised beagle dogs of 13 to 15 kg body weight. Myocardial electrocardiograms were simultaneously recorded from 31 electrodes located on the left and right ventricular surfaces of the in situ canine heart. Recordings were obtained over a single cardiac cycle during rapid ventricular pacing at the maximum following frequency. Computer assisted measurements of activation time, activation-repolarisation interval, and repolarisation time were performed and the heterogeneity of these measurements calculated. Measurements were performed before treatment and after each incremental intravenous dose of dofetilide (3, 10, 30, and 100 micrograms.kg-1), quinidine (1, 3, and 10 mg.kg-1), or saline vehicle. RESULTS: Dofetilide increased repolarisation time via a selective prolongation of activation-repolarisation interval, activation time being unchanged. It reduced the heterogeneity of repolarisation time and activation-repolarisation interval, heterogeneity of activation time being unchanged. Quinidine increased repolarisation time by a non-selective increase of both activation-repolarisation interval and activation time. It increased the heterogeneity of activation times which offset a decrease in heterogeneity of activation-repolarisation intervals to produce no change in heterogeneity of repolarisation times. CONCLUSIONS: Dofetilide, but not quinidine, reduces pacing induced asynchrony of repolarisation in the canine heart and this effect may contribute to its antiarrhythmic activity.

Animals↗
PubMed1990

The government white paper: threat or challenge?

Medical education should provide the essential basis for a comprehensive health service. Postgraduate training in the hospital sphere is manifestly inadequate, particularly in the early postqualification years. It is in sharp contrast to the excellence of vocational training for general practice. The White Paper presents a challenge and a window of opportunity to redress this imbalance and calls for a clear educational strategy crossing all administrative, professional and political boundaries.

Education, Medical, Graduate↗
PubMed1989

Senior house officers and their training. I. Personal characteristics and professional circumstances.

To assess the experience and perceptions of training of senior house officers in medicine a population survey of senior house officer training was conducted on senior house officers, registrars, senior registrars, and consultants in six medical specialties in South East Thames region by interview and postal questionnaire. The overall response rate was 72%, varying from 62% to 83% according to status and from 61% to 80% according to specialty. Although most of the 226 senior house officer respondents were aged 28 or under (168/225), had been qualified for four years or less (168/225) and were British (176/223), a quarter were older and had been qualified for five years or more; in all, 17 other nationalities were represented. Twenty two were aged over 33, and 17 had been qualified for more than 10 years. Thirty five senior house officers worked more than the mode of the distribution of duty rotas (one in three). Among postgraduate qualifications achieved or pursued, those related to general practice were highly represented (164 examinations); 111 senior house officers intended becoming general practitioners, 63 non-teaching hospital consultants, and 34 university or NHS teaching staff. Analysis of career progression showed that an appreciable number (31/221) had had more than three senior house officer posts. The findings indicate that the main implications for training and education are time for study, careers advice, and revision of educational programmes.

Adult↗
PubMed1989

Senior house officers and their training. II. Perceptions of service and training.

Aspects of teaching and learning at senior house officer level in South East Thames region were investigated by analysis of the responses of consultants, senior registrars, registrars, and senior house officers to a postal questionnaire. Responses to sections about who teaches senior house officers, how senior house officers learn, and the relation between the service and training elements of these posts varied significantly, according to the status of the respondents; certain grades commonly overestimated their own contribution when compared with the estimates of the other grades. Although the replies of senior house officers showed that they were taught by various grades, 47% of this group did not regard the consultant as their main teacher. Senior registrars and registrars rather than consultants were regarded by senior house officers as best at teaching (63% v 48% respectively). Consultants and registrars were considered to require more commitment to training, personal educational training, and to be more approachable. Inquiry about teaching methods used most by senior house officers showed absence of a systematic approach to training. Only about half of senior house officers cited ward rounds with consultants. Views on the relation between training and service were significantly different among grades, but there was general dissatisfaction. Overall, the findings disclosed the ineffectiveness of senior house officer training posts. This arises from lack of a clear distinction between training and service elements, of educational training for teachers, of a clear contractual obligation to teach im the consultant grade, and of allotted time for training and study for the teachers and senior house officers respectively. Reversal of these current trends is needed for senior house officer posts to fulfil their main training function.

Attitude of Health Personnel↗
PubMed1989

The role of polyfusomes in generating branched chains of cystocytes during Drosophila oogenesis.

Three-dimensional models were constructed utilizing the information gained from electron micrographs of serial sections of two clones of cystocytes undergoing their terminal divisions. In each clone a polyfusome connected all eight cystocytes together. Each of the spindles was oriented so that one pole touched the polyfusomes, while the other pointed away from it. This positioning of spindles ensures that one cell of each dividing pair retains all previously formed canals, while the other receives none. The two cells that eventually come to contain the maximum number of canals and fusomal material are the ones that differentiate as pro-oocytes, while the others become nurse cells. The orientation of each spindle suggests that the polyfusome formed at one division determines the placement of the cytoskeletal fibers that anchor the spindles formed at the next division. There is a centripetal gathering together of new canals following each cycle of cystocyte division, which is thought to result from the subsequent contraction of the polyfusomal system. Females homozygous for the otu1 mutation are characterized by ovarian tumors, which result when germarial cystocytes undergo supernumerary divisions and fail to differentiate into either nurse cells or oocytes. An analysis of electron micrographs taken of serially sectioned, mutant germaria showed that most germ cells were single or belonged to clusters of two or three interconnected cells. Therefore otu1 cystocytes are unable to undergo a sustained series of arrested cleavages. These cystocytes contain fusomal material that shows ultrastructural differences from normal polyfusomes. We conclude: 1) that a normal polyfusomal system is a necessary prerequisite for the production of a branched chain of cystocytes and for their subsequent differentiation into pro-oocytes and nurse cells; and 2) that a product encoded by the otu+ gene is essential for the construction of a functional polyfusome.

Animals↗
PubMed1988

Multiplicity of functions for the otu gene products during Drosophila oogenesis.

The ovarian tumor gene behaves as if it encodes a product (OGP), which is required during several early steps in the transformation of oogonia into functional oocytes. Seventeen ethyl methane sulfonate-induced mutations have been studied, and their mutant phenotypes can be explained as graded responses by individual germ cells to different levels of OGP synthesized by the mutant germ cells themselves. The lowest and highest levels of OGP appear to be produced by otu10 and otu14, respectively. The 15 mutants with intermediate OGP levels are temperature sensitive; subnormal temperatures improve ovarian development, while above-normal temperatures suppress it. A subgroup of these mutants are unable to form a system of actin microfilament bundles in the cortical cytoplasm of their nurse cells during stage 10B, and these defective nurse cells are unable to transport their cytoplasm to the oocyte, as normally happens between stages 10B and 12. In addition to its role in the actin-mediated transport of nurse cell cytoplasm, OGP also appears to alter the morphology of giant polytene chromosomes, which form as the nurse cells undergo endocycles of DNA replication. Genetic evidence suggests that otu also encodes a second product (SP) that is utilized late in oogenesis. SP is required for the synthesis in the ooplasm of glycogen-rich, beta yolk spheres. Products of the otu gene also play a vital but unknown role in embryogenesis.

Aging↗