Biomedical subjects

C Hartley

Publications and source records attributed to C Hartley.

At least 19 recordsLinked to original sources

PubMed1998

Primary non-Hodgkin's lymphoma of the larynx in an AIDS patient.

A case of primary non-Hodgkin's lymphoma of the larynx in an AIDS patient is presented with a review of the literature. Non-Hodgkin's lymphomas in AIDS patients are common but the primary laryngeal presentation is very rare. The symptoms usually include dysphonia and progressive airway obstruction requiring tracheostomy. As with laryngeal non-Hodgkin's laryngeal lymphomas in non-HIV positive patients the majority are of B cell lineage and respond well to radiotherapy. Our patient had a high grade lymphoma of B cell lineage which showed a good response to radiotherapy. The role of chemotherapy and surgery is not yet established. We suggest that the diagnosis of AIDS should not influence the management of these patients unless the individual is in the terminal disease stage.

Adult↗

PubMed1998

Marrow repopulating cells in mobilized PBPC can be serially transplanted for up to five generations or be remobilized in PBPC reconstituted mice.

We have evaluated the durability of engraftment and the potential of remobilization in mice reconstituted with mobilized peripheral blood progenitor cells (PBPC). Female mice which had been reconstituted with cytokine-mobilized PBPC from male donors were serially transplanted into second, third, fourth and fifth lethally irradiated female recipients at intervals of 6-10 months. Male-derived hematopoiesis was determined in recipient mice at each serial transplantation. Male-positive CFCs were detected after 5 passages for 45 months, but declined from >95% at passage 1 to 74% at passage 2, 33% at passage 4, and 28% at passage 5. Long-term survival also declined from 97% at passage 2 to 53% at passage 4, and 27% at passage 5. The results demonstrated that mobilized PBPC were able to provide engraftment for more than 45 months, but the engraftment provided by mobilized PBPC decreased at each serial passage. In addition, mice reconstituted with mobilized PBPC (at 1 year post transplantation) were treated with the same cytokines as in the primary mobilization (remobilization). The remobilized PBPC were harvested and transplanted into lethally irradiated secondary recipients. Male-derived CFCs were evaluated at 20 months post transplantation. Mice transplanted with PBPC remobilized with rhG-CSF or rhG-CSF plus rrSCF-PEG showed 70% and 89% male-positive CFCs respectively, demonstrating that mice reconstituted with mobilized PBPC could be remobilized and that the remobilized PBPC were also capable of providing long-term hematopoietic reconstitution. Our studies demonstrated that mobilized PBPC have extensive proliferative or self-renewal capacity to provide durable engraftment and that marrow repopulating cells in PBPC reconstituted mice can be remobilized, suggesting that patients who relapse after PBPC transplantation may be remobilized for a second transplantation to support additional chemotherapy.

Animals↗

PubMed1998

Microbiology and antibiotic treatment of head and neck abscesses in children.

The clinical data, microbiological results and antibiotic treatment of 65 children who have required incision and drainage of suppurative head and neck abscesses was retrospectively investigated with the aim of developing a more effective clinical protocol of treatment, improving speed of resolution and rationalizing the need for surgical intervention. A positive culture grew in 78% of children and of these 45% were Staphylococcus aureus, 9% Streptococcus pyogenes, and 8% atypical mycobacteria. Only 3% of the samples grew anaerobes. All isolates of S. aureus were sensitive to Flucloxacillin and all isolates of S. pyogenes were sensitive to penicillin. All anaerobes were Metronidazole sensitive. In 40% of the children there were no localizing symptoms which could guide the treatment, therefore we recommend Flucloxacillin and Metronidazole as the antibiotic regimen of choice in acute suppurative lymphadenitis. The increasing incidence of atypical mycobacterial lymphadenitis is noteworthy.

Abscess↗

PubMed1997

Chronic expression of murine flt3 ligand in mice results in increased circulating white blood cell levels and abnormal cellular infiltrates associated with splenic fibrosis.

The effect of chronic expression of flt3 ligand (FL) on in vivo hematopoiesis was studied. Retroviral vector-mediated gene transfer was used in a mouse model of bone marrow transplantation to enforce expression of mouse FL cDNA in hematopoietic tissues. As early as 2 weeks posttransplantation, peripheral blood white blood cell counts in FL-overexpressing recipients were significantly elevated compared with controls. With the exception of eosinophils, all nucleated cell lineages studied were similarly affected in these animals. Experimental animals also exhibited severe anemia and progressive loss of marrow-derived erythropoiesis. All of the FL-overexpressing animals, but none of the controls, died between 10 and 13 weeks posttransplantation. Upon histological examination, severe splenomegaly was noted, with progressive fibrosis and infiltration by abnormal lymphoreticular cells. Abnormal cell infiltration also occurred in other organ systems, including bone marrow and liver. In situ immunocytochemistry on liver sections showed that the cellular infiltrate was CD3+/NLDC145+/CD11c+, but B220- and F4/80-, suggestive of a mixed infiltrate of dendritic cells and activated T lymphocytes. Infiltration of splenic blood vessel perivascular spaces resulted in vascular compression and eventual occlusion, leading to splenic necrosis consistent with infarction. These results show that FL can affect both myeloid and lymphoid cell lineages in vivo and further demonstrate the potential toxicity of in vivo treatment with FL.

Animals↗

PubMed1997

An analysis of the effects of combined treatment with rmGM-CSF and PEG-rHuMGDF in murine bone marrow transplant recipients.

We have studied the potential of combination growth factor treatment with GM-CSF and megakaryocyte growth and development factor (MGDF) to stimulate hematopoietic recovery in mice following bone marrow transplantation. More rapid recovery of neutrophils occurred in mice treated with recombinant murine (rm)GM-CSF plus pegylated recombinant human (PEG-rHu)MGDF than carrier treated controls, however this recovery was equivalent to the effect of treatment with rmGM-CSF alone. PEG-rHuMGDF stimulated a more rapid recovery of platelets with no effect on neutrophil recovery. At the two tested doses of rmGM-CSF (72 and 200 microg/kg/day) the platelet recovery was inferior to that in carrier treated mice. Also, the addition of rmGM-CSF to PEG-rHuMGDF had a dose-related negative impact on platelet recovery compared to PEG-rHuMGDF alone. These data suggest that the use of combination therapy in some clinical indications may lead to unexpected results. Furthermore, careful dosage studies may be necessary to identify the full potential of combined growth factors to obtain additive or synergistic effects on multilineage hematopoietic reconstitution in vivo.

Animals↗

PubMed1997

Otorhinolaryngological training in Europe--a comparative study.

Postgraduate training in the United Kingdom is undergoing radical changes following the 'Calman Report'. Commissioned in response to a European Union (EU) Directive, this contained recommendations to allow reciprocal recognition of all EU trained specialists. We present the findings of a postal questionnaire sent to representatives of the European Federation of Oto-Rhino-Laryngological Societies and the otolaryngology professors of the UK and Ireland with a response rate of 62.7%. Aspects assessed included clinical and surgical experience, examinations, teaching, research, length, regulation and perception of training. The programmes share similar teaching and research experience but substantial differences exist in most other areas. The accredited UK trainee has a much wider clinical and surgical repertoire than those from the Continent. Greek trainees were trained to the lowest minimum standard. The requirements of a training system are largely determined by the level of clinical experience and surgical skill required by an independent specialist in a given country.

Europe↗

PubMed1997

Confirmation of the presence of Mycobacterium tuberculosis and other mycobacteria in mycobacterial growth indicator tubes (MGIT) by multiplex strand displacement amplification.

Multiplex strand displacement amplification (mSDA) is capable of amplifying three distinct DNA sequences simultaneously. These include sequences present in most genera of mycobacteria, a sequence specific for Mycobacterium tuberculosis, and an internal control. mSDA was used to detect the presence of these target sequences in 154 (72 positive, 76 negative, and 6 failed) clinical specimens cultured in the mycobacterial growth indicator tube (MGIT) system. A wide variety of specimen types were processed and cultured. Once these cultures were deemed positive by MGIT fluorescence or were deemed negative after 8 weeks of incubation, MGIT culture aliquots were processed for mSDA analyses. A chemiluminescent microwell assay was used to detect the amplified products. The procedure was relatively simple and took less than 6 h to complete. The sensitivity of mSDA for detecting acid-fast bacilli was 96.4% compared to that of MGIT culture. Sensitivity and specificity were 97.2 and 96.1%, respectively, when all clinical criteria were considered. mSDA was shown to be a rapid and effective method for confirming the presence of M. tuberculosis and other mycobacteria in positive MGIT cultures.

Bacterial Typing Techniques↗

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↗