Biomedical subjects

C Hartley

Publications and source records attributed to C Hartley.

At least 37 records · Page 2Linked to original sources

PubMed1996

Megakaryocyte growth and development factor accelerates platelet recovery in peripheral blood progenitor cell transplant recipients.

We have investigated the potential of PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a molecule related to thrombopoietin (mpl ligand or TPO) in minimizing the thrombocytopenia associated with hematopoietic ablation and peripheral blood progenitor cell (PBPC) transplant. Irradiated mice that received PBPC mobilized by PEG-rHuMGDF or granulocyte colony-stimulating factor (G-CSF) had a reduced number of thrombocytopenic days with platelets below 100 x 10(6) per mL of blood. Recipients of unmobilized PBPC had a 9 day thrombocytopenic phase which was shortened to 7 days if they were given granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPC. This was further reduced to 2 or 3 days of thrombocytopenia in recipients of G-CSF- or PEG-MGDF-mobilized PBPC. Despite our observation that PEG-rHuMGDF is a relatively modest stimulator of the mobilization of myeloid progenitors to the blood, MGDF-mobilized PBPC do effect accelerated recovery of platelets after transplantation. However, the most effective use of PEG-rHuMGDF is when it is given during the recovery phase after PBPC transplantation to hematopoietically ablated mice. Posttransplant treatment with PEG-rHuMGDF reduces thrombocytopenia to a single day or less, in recipients of most types of PBPC. Mice that were treated during the first 2 weeks after PBPC transplant with PEG-rHuMGDF had 1 thrombocytopenic day compared to 9 days in carrier-treated recipients of unmobilized PBPC and 2 to 3 days in carrier-treated recipients of the optimally mobilized PBPC from G-CSF or G-CSF/PEG-rHuMGDF treated donors. In groups where PEG-rHuMGDF was included in the mobilization protocol and used to treat recipients as well thrombocytopenia was effectively eliminated. These data show that PEG-rHuMGDF is a highly effective agent in eliminating the thrombocytopenia associated with PBPC transplantation.

Animals↗

PubMed1996

The intracellular fate of apolipoprotein E is tau dependent and apoe allele-specific.

The apolipoprotein E (apoE) gene has been identified as a susceptibility gene for Alzheimer's disease, although the mechanism whereby apoE exerts this effect has not been determined. The aim of this study was to examine the intracellular fate of apoE and we demonstrate that in mammalian cells-transiently expressing tau and the low density lipoprotein receptor, apoE is taken up from cerebrospinal fluid (CSF) and apoE3, but not apoE4, reaches the cytoplasm. This isoform difference in the intracellular distribution of apoE is dependent upon tau expression and, although tau phosphorylation was not affected by apoE, these results suggest that apoE interactions with the cytoskeleton might be important in the molecular pathogenesis of Alzheimer's disease.

Alleles↗

PubMed1996

Cardiac and regional hemodynamic interactions between halothane and nitric oxide synthase activity in dogs.

BACKGROUND: In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs. METHODS: Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA. RESULTS: In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction. CONCLUSIONS: Halothane minimally interferes with the systemic and regional hemodynamic consequences of nitric oxide synthase blockade. The nature and magnitude of the interaction depend on the territory in which they occur.

Anesthetics, Inhalation↗

PubMed1996

The incidence of bacteria in middle ear effusions.

Otitis media with effusion (OME) is a common condition in paediatric ENT practice. Whilst surgical management is in many cases the mainstay of treatment for resistant OME, the use of antibiotics has been advocated by some authorities. Over one quarter of middle ear effusions analysed in this study contained potentially pathogenic bacteria. Antibiotics may be of value in the treatment of OME in these children.

Anti-Bacterial Agents↗

PubMed1996

Comparison of mycobacteria growth indicator tube with BACTEC 460 for detection and recovery of mycobacteria from clinical specimens.

We compared the Mycobacteria Growth Indicator Tube (MGIT) system with the BACTEC 460 (B460) and Lowenstein Jensen (LJ) systems for the recovery of mycobacteria (acid-fast bacteria [AFB]) from 1,441 clinical specimens. Excluding 13 isolates of Mycobacterium gordonae, 178 significant AFB isolates were recovered from 113 patients. Isolates (119) of the Mycobacterium avium complex (MAC) accounted for 67% of all isolates, while isolates (30) of the Mycobacterium tuberculosis complex (MTB) accounted for 17% of isolates. The MGIT system recovered 98 (82%) MAC and 27 (90%) MTB isolates, while the B460 system recovered 101 (85%) MAC and 28 (93%) MTB isolates and the LJ system recovered 91 (76%) MAC and 25 (83%) MTB isolates. Overall, the MGIT system recovered 152 isolates of AFB (85.4% sensitivity), and the B460 and LJ systems recovered 151 (84.8% sensitivity) and 137 (76.9% sensitivity) AFB isolates, respectively. The recoveries of AFB with combinations of media were as follows: MGIT + LJ, 93.2%; B460 + LJ, 92.1%; and MGIT + B460, 96.6%. Although the sensitivity of MGIT was equivalent to that of B460, MGIT required a longer incubation (median, 11 days) than did B460 (median, 8 days) to become positive (P < 0.05).

Cell Culture Techniques↗

PubMed1996

Neuroendocrine carcinoma of the larynx.

Neuroendocrine carcinomas (NEC) of the larynx are rare. The key to diagnosis is therefore an increased awareness of such lesions amongst otolaryngologists and pathologists. A precise histological diagnosis is crucial, as the management is different for each NEC sub-type. Advances in immunohistochemistry have been a great help in this respect. We report a typical case of large cell NEC (atypical carcinoid) and highlight the clinical pointers to the histological diagnosis.

Carcinoma, Neuroendocrine↗

PubMed1995

Chronic exposure to retroviral vector encoded MGDF (mpl-ligand) induces lineage-specific growth and differentiation of megakaryocytes in mice.

Megakaryocyte growth and development factor (MGDF) has recently been identified as a ligand for the c-mpl receptor. Using retroviral-mediated gene transfer, MGDF has been overexpressed in mice to evaluate the systematic effects due to chronic exposure to this growth factor. MGDF overexpressing mice had more rapid platelet recovery than control mice after transplantation. Following this recovery, the platelet levels continued increasing to fourfold to eightfold above normal baseline levels and remained elevated (five-fold above control mice) in these animals, which are alive and well at more than 4 months posttransplantation. Increased megakaryocyte numbers were detected in a number of organs in these mice including bone marrow, spleen, liver, and lymph nodes. Prolonged overexpression of MGDF led to decreased marrow hematopoiesis, especially erythropoiesis, with a shift to extramedullary hematopoiesis in the spleen and liver. All the MGDF overexpressing mice analyzed to date developed myelofibrosis and osteosclerosis, possibly induced by megakaryocyte and platelet produced cytokines. No significant effect on other hematopoietic lineages was seen in the MGDF overexpressing mice, showing that the stimulatory effect of MGDF in vivo is restricted to the megakaryocyte lineage.

Animals↗

PubMed1995

Peripheral blood progenitor cells mobilized by recombinant human granulocyte colony-stimulating factor plus recombinant rat stem cell factor contain long-term engrafting cells capable of cellular proliferation for more than two years as shown by serial transplantation in mice.

Mobilized peripheral blood progenitor cells (PBPC) have been shown to provide rapid engraftment in patients given high-dose chemotherapy. PBPC contain cells with long-term engraftment potential as shown in animal models. In this study we have further analyzed mobilized PBPC for their ability to support serial transplantation of irradiated mice. Transplantation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) plus recombinant rat stem cell factor (rrSCF) mobilized PBPC resulted in 98% donor engraftment of primary recipients at 12 to 14 months post-transplantation. Bone marrow (BM) cells from these primary recipients were harvested and transplanted into secondary recipients. At 6 months posttransplantation, all surviving secondary recipients had donor engraftment. Polymerase chain reaction (PCR) analysis showed greater than 90% male cells in spleens, thymuses, and lymph nodes. Myeloid colonies from BM cells of secondary recipients demonstrated granulocyte/macrophage colony-forming cells (GM-CFC) of male origin in all animals. In comparison, transplantation of rhG-CSF mobilized PBPC resulted in decreased male engraftment in secondary recipients. BM cells from secondary recipients, who originally received PBPC mobilized by the combination of rrSCF and rhG-CSF, were further passaged to tertiary female recipients. At 6 months posttransplantation, 90% of animals had male-derived hematopoiesis by whole-blood PCR analysis. These data showed that PBPC mobilized with rhG-CSF plus rrSCF contained cells that are transplantable and able to maintain hematopoiesis for more than 26 months, suggesting that the mobilized long-term reconstituting stem cells (LTRC) have extensive proliferative potential and resemble those that reside in the BM. In addition, the data demonstrated increased mobilization of LTRC with rhG-CSF plus rrSCF compared to rhG-CSF alone.

Animals↗

PubMed1995

Cryotherapy in the treatment of nasal obstruction: indications in adults.

Cryotherapy is an established method of treating hypertrophic obstructive inferior turbinates. The long-term effectiveness of the technique is assessed in this study, using the need for alternative nasal surgery as an objective way of distinguishing success from failure. Over 50 per cent of patients with obstructive symptoms, including those with minor septal deviation or allergy derived lasting benefit from the technique. Cryotherapy is an effective means of treating nasal obstruction due to mucosal hypertrophy of the turbinates and may replace the need for more radical surgery.

Adolescent↗

PubMed1995

Non-cholesteatomatous suppurative otitis media: facial nerve palsy in an immunocompromised patient.

A 47-year-old man developed a complete facial nerve palsy secondary to non-cholesteatomatous suppurative otitis media. At operation, this was seen to be due to destruction of the nerve from halfway along the horizontal segment to a point just distal to the second genu. The history of recent renal transplantation and subsequent immunosuppression was judged to be significant in the pathogenesis of the palsy.

Facial Paralysis↗

PubMed1995

Endoscopic balloon dilatation of subglottic stenosis.

Children with subglottic stenosis present a challenging problem to otolaryngologists. In many cases, a tracheostomy is necessary to safeguard the airway, but morbidity and mortality in the tracheostomized child may be significant. Therefore attempts to improve the airway by endoscopic means are often made; unfortunately, these have a variable success rate. Recent encouraging results in the use of balloon dilatation for subglottic stenosis led us to the successful use of this technique in a child whose stenosis had not responded to conventional endoscopic techniques. The reasons for the success are discussed.

Catheterization↗

PubMed1995

The Apache II scoring system in neurosurgical patients: a comparison with simple Glasgow coma scoring.

In order to compare the predictive value of the Apache II, the Glasgow Coma Scale and Revised Trauma Scoring systems in relation to outcome in a neurosurgical department high dependency unit (HDU), all 109 patients entering the unit under the care of one consultant were studied. All patients in the HDU were self-ventilating, so that motor responses were not suppressed by muscle relaxants or sedation. Initial Minimum and Maximum Glasgow Coma Scale Scores, Revised Trauma Score, Apache II and the Apache minus neurological weighting (Apache-NW) scores, were compared as predictors of outcome (as assessed by the Glasgow Outcome Score at 6 months). Twenty-eight patients had a bad outcome, i.e. Glasgow Outcome Scores 1-3, and 72 individuals a good outcome, i.e. scores 4 or 5. Statistical analysis was by the Spearman Ranked Correlation Test, and comparison of Receiver Operational Characteristics Curves. Data were complete on 100 patients (91.7%) and show the Maximum Glasgow Coma Score, followed by the Apache II score, as the best predictors of outcome analysed. This was also true if all patients except those with head injury were analysed as a group. All scoring systems were significantly better predictors of outcome in the head injured patient. For this group, Apache II had an outcome predictive value of 97% compared with 93% for initial and 95% for minimum GCS. Removing the neurological weighting from Apache II weakened its predictive ability in all patients, emphasizing that it is the neurological status of the patient which best predicts overall functional outcome. Apache II data are also much more time-consuming to collect than GCS data.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Injuries↗

PubMed1995

External ear canal cholesteatoma. Case report.

External ear canal cholesteatoma is a rare condition in otologic practice. A case in a 43-year-old woman is presented in which despite the extensive nature of the lesion, minimal symptoms and absence of signs delayed diagnosis. The cause of the lesion and its treatment are discussed.

Adult↗

PubMed1995

Cochlear reimplantation.

Since its inception in 1988 the Cochlear Implant Programme in Manchester has successfully implanted 69 adults and 23 children. Of these 92 procedures, three patients have undergone revision surgery with the insertion of either a new implant or re-positioning of the existing device. We examine the circumstances that lead to the need for reimplantation in these patients, discuss the technical aspects of revision surgery together with the functional results of such procedures.

Adult↗

PubMed1995

CT and MR appearance of otolaryngologic packing materials.

PURPOSE: To examine the CT and MR appearances of four packing materials commonly used in otolaryngologic surgery. METHODS: The CT and MR appearances of bismuth and iodoform paraffin paste, aqueous betadine gauze, calcium sodium alginate, and triadocortyl cream were examined. CT attenuation values were measured using phantoms containing packing materials. MR characteristics were examined by packing the external auditory meati of volunteers. Two illustrative case reports also are presented. RESULTS: Bismuth and iodoform paraffin paste has a high CT attenuation (> 3000 Hounsfield units) resulting in severe image degradation attributable to streak artifact. Aqueous betadine gauze was of high attenuation (258 Hounsfield units; SD, 16.5) but did not cause image degradation. The attenuation values of calcium sodium alginate and triadocortyl creme coincided with those of muscle and fat, respectively. On MR, calcium sodium alginate and bismuth and iodoform paraffin paste had imaging characteristics similar to muscle and aqueous betadine gauze had appearances similar to bone marrow. Triadocortyl cream had a high signal equal to that of fat on T1-weighted images but a lower signal similar to bone marrow on T2-weighted images. CONCLUSIONS: The presence of bismuth and iodoform paraffin paste can give rise to clinically important image degradation on CT. More seriously, residual packing material may be misinterpreted as infection or tissue necrosis.

Adolescent↗

PubMed1995

Etiology of hearing loss and cochlear computed tomography: findings in preimplant assessment.

Patients being considered for cochlear implantation undergo, of necessity, a wide-ranging selection process, of which imaging of the temporal bone to assess cochlear patency is an important part. We have studied the correlation between the results of computed tomography (CT) imaging of the cochlea and the cause of hearing loss in this group of patients. The CT scans of 105 patients were reviewed. Of these, 74 (70%) were normal, with the commonest abnormalities being labyrinthitis ossificans in 14 (13.3%) cases and capsular rarefaction in 10 (9.5%) cases. A congenital abnormality was seen in 4 (3.8%) cases and temporal bone fractures in 2 (1.9%) cases; 1 patient had previously undergone a labyrinthectomy. In 25 patients the cause of the hearing loss was known to be meningitis. Of these patients, 15 had normal scans and 10 showed labyrinthitis ossificans. Of note is that none of the 6 patients with tuberculous meningitis had abnormal scans. There was a high correlation between a rarefied capsule on CT imaging and a diagnosis of otosclerosis, with 6 out of 7 otosclerosis patients demonstrating this abnormality. Evidence of a previous temporal bone fracture was seen on the scans of only 2 out of 6 patients in whom the cause of deafness was thought to be severe head injury.

Cochlea↗

PubMed1995

Cochlear reimplantation.

Since its inception in 1988, the Cochlear Implant Programme in Manchester has successfully implanted 61 adults and 15 children. Of these 76 patients, 3 have undergone revision surgery, and these cases are presented. One patient was a 43-year-old blind man who underwent routine implantation with a Nucleus device. Six weeks after implantation the patient experienced sudden device failure following an electric shock from a domestic appliance. The patient was reimplanted with a similar device 3 weeks later and is making good progress. Assessment of the original implant showed a failure of one of the capacitors in the receiver-stimulator circuit. The second patient was a 51-year-old woman who underwent routine implantation with a Nucleus 22-channel device. The patient's audiologic performance fluctuated, and 14 months after the original procedure the patient was reimplanted. Analysis by the manufacturer suggested that the original implant was unstable at higher temperatures. The third patient, a 55-year-old woman, was implanted with an Ineraid multichannel device into the right cochlea. A postoperative radiograph showed the implant to be incorrectly positioned, and the procedure was revised 4 weeks later. Here it was found that the electrode system was running across the promontory, toward the eustachian tube orifice. This was reimplanted with satisfactory results.

Adult↗

PubMed1994

Mobilization of long-term hematopoietic reconstituting cells in mice by the combination of stem cell factor plus granulocyte colony-stimulating factor.

In this study, we have compared the ability of recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone and the combination of low doses of recombinant rat pegylated stem cell factor (rrSCF-PEG) plus rhG-CSF to mobilize peripheral blood progenitor cells (PBPCs) with long-term engrafting potential. Female recipient irradiated mice were transplanted with PBPCs from male mice that were mobilized with rhG-CSF alone (group A) or rrSCF-PEG plus rhG-CSF (group B). As previously shown, greater short-term survival resulted in group B compared with group A, with 80% and 40% survival at 30 days posttransplant, respectively. Both groups of animals showed long-term donor-derived engraftment in greater than 95% of animals, as determined by quantitative specific polymerase chain reaction amplification of a Y chromosome sequence from whole blood of the mice at 6 to 12 months posttransplantation. Analysis of individual granulocyte-macrophage colonies, picked up from semisolid methylcellulose culture of bone marrow cells from transplanted mice, resulted in detection of donor-derived DNA in 98% of colonies from group B mice compared with 81% from group A mice. These data show that cells with long-term potential are mobilized by rhG-CSF alone and the combination of rrSCF-PEG plus rhG-CSF. Furthermore, an increased number of cells with short-term and long-term engraftment potential was obtained with rrSCF-PEG plus rhG-CSF compared with rhG-CSF alone.

Animals↗