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Biomedical subjects

C Harrison

Publications and source records attributed to C Harrison.

At least 19 recordsLinked to original sources

Bioethics for clinicians: 9. Involving children in medical decisions.

Medical decisions involving children raise particular ethical issues for physicians and other members of the health care team. Although parents and physicians have traditionally made most medical decisions on behalf of children, the developing autonomy of children is increasingly being recognized in medical decision-making. This poses a challenge for physicians, who must work with the child's family and with other health care practitioners to determine the child's role in decision-making. A family-centred approach respects the complex nature of parent-child relationships, the dependence and vulnerability of the child and the child's developing capacity for decision-making.

Adolescent

Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression.

The incidence of cervical adenocarcinomas in young women over the last two decades has increased. Even with increasing knowledge of the role of human papillomavirus in the etiology of adenocarcinoma of the cervix, there is a paucity of data concerning the genetic and epigenetic factors that contribute to the histologic features and biologic behaviors of these tumors. Lactoferrin is a basic glycoprotein found in human milk, secondary granules of neutrophils, and many body secretions, and it has been associated with carcinogenesis of the endometrium, breast, and lymphoid systems. In this study, we examined the expression of lactoferrin in normal human endocervical epithelium and in cervical adenocarcinomas in relation to proliferative index, steroid receptor status, p53 protein expression, and apoptosis. Immunohistochemical and in situ studies demonstrated that lactoferrin protein and mRNA were strikingly downregulated upon neoplastic transformation of the endocervix as early as in adenocarcinoma in situ when compared with the prominent expression exhibited by the normal cervical epithelium. Furthermore, neoplastic transformation of endocervical epithelial cells was accompanied by a pronounced stimulation of proliferation and a substantial reduction in the expression of the estrogen and progesterone receptors and p53 but little or no change in the number of apoptotic cells. In conclusion, we identified lactoferrin as a novel cancer-specific marker of endocervical adenocarcinomas that may be useful in the early detection of the disease, prediction of prognosis, and the development of new therapeutic modalities.

Adenocarcinoma

Lens clarity after lens-sparing vitrectomy in a pediatric population.

PURPOSE: The purpose of the study is to assess lens clarity after pediatric lens-sparing vitrectomy. METHODS: The study offers a retrospective analysis of 85 eyes of 77 pediatric patients who underwent lens-sparing vitrectomy for tractional retinal detachment or opaque media, and who were observed for 10 to 55 months. RESULTS: A total of 57 eyes maintained clear lenses at last follow-up examination. Cataract was found in 13 (15%) of the 85 eyes. Fifteen eyes (18%) had undergone lens removal as part of reoperation for progressive ocular disease. CONCLUSION: Sixty-seven percent of pediatric lenses remained clear after lens-sparing vitrectomy.

Cataract

Diagnostic utility of bone marrow sampling in HIV positive patients.

OBJECTIVE: To evaluate the diagnostic utility of bone marrow (BM) sampling in HIV positive patients. DESIGN: Retrospective cohort analysis. SETTING: Specialist HIV/AIDS service in London. SUBJECTS: 215 consecutive HIV infected patients undergoing 246 BM samplings for investigation of pyrexia without localising signs, haematological abnormalities, or staging/investigation of lymphoma. MAIN OUTCOME MEASURE: Diagnostic yield from (and impact on management of) BM sampling. RESULTS: Of 122 BM samples taken to investigate pyrexia, 33 (27%) revealed the cause on microscopy: unexpected lymphoma in seven (6%), mycobacteriosis in 25 (20%), and toxoplasmosis in one (1%). Marrow infiltration was confirmed in 11 of 38 BM samples taken for staging/investigation of lymphoma/leukaemia. In afebrile patients, of 22 with pancytopenia, BM samples showed HIV associated changes in 17 and specific diagnoses in five (mycobacterial infection in three, haemophagocytic syndrome in one, and megaloblastic change due to vitamin B-12 deficiency in one); of 21 with isolated thrombocytopenia, 20 (95%) BM samples showed immune thrombocytopenic purpura to be the cause and the remaining patient had BM changes of aplasia; of 29 with isolated anaemia, 28 had BM changes of HIV associated dysplasia/erythroid dysplasia and one had unsuspected iron deficiency; all 10 with isolated leucopenia/neutropenia had BM changes ascribed to HIV infection exacerbated by concurrent sepsis or medication; of four BM samples taken for other reasons, one showed mycobacterial infection. CONCLUSIONS: BM sampling has diagnostic utility in HIV infected patients with pyrexia without localising signs, pancytopenia, and staging/investigation of lymphoma; this test has little value in the investigation of afebrile patients with isolated thrombocytopenia, anaemia, or leucopenia as HIV is usually the underlying cause.

AIDS-Related Opportunistic Infections

Weight loss associated with HIV seroconversion among injection-drug users.

To describe symptoms associated with human immunodeficiency virus (HIV) seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a study design that included recall every 3 months to collect symptom histories using a structured questionnaire. Eleven HIV seroconversions were observed in 621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR. Cox regression analysis showed age < or = 35 years to be a significant risk factor for HIV seroconversion after controlling for gender, race, and the frequency of drug injection. An embedded case-control analysis then compared symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit number-matched controls who remained HIV seronegative for > or = 3 months longer than the HIV-seroconverters. Multivariate case-control analysis adjusted for injection frequency yielded significant associations of HIV seroconversion with histories of weight loss > or = 4.5 kg (seven of 11 cases; odds ratio [OR] = 11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases; OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV-seropositive study visit. We conclude that histories of recent symptoms reported by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting IDUs, and weight loss may be particularly common among IDUs experiencing primary HIV infection.

Adult

Induction of the chemotactic S100 protein, CP-10, in monocyte/macrophages by lipopolysaccharide.

The murine S100 protein CP-10 is a potent chemotactic factor for murine and human myeloid cells in vivo and in vitro. This is the first report describing regulations of the CP-10 gene by a proinflammatory stimulus, lipopolysaccharide (LPS), in cells of the monocyte/macrophage lineage. Murine monocyte/macrophage-like WEHI 265 and RAW 264.7 cells preexposed to 5 to 50 ng/mL LPS expressed significant levels of CP-10 mRNA 4 hours, and maximal at 20 hours, after a secondary LPS challenge. This was accompanied by increasing levels of cell-associated and released CP-10 protein. In contrast, a single dose of LPS upregulated CP-10 mRNA in elicited peritoneal macrophages, whereas mRNA and protein levels decreased following LPS challenge. The state of macrophage differentiation may control responsiveness as LPS had no effect on CP-10 basal levels in bone marrow derived macrophages. LPS-induced CP-10 expression was controlled at the transcriptional level and nuclear run-on and protein synthesis inhibition assays indicated that LPS priming and challenge of RAW cells occurred via distinct pathways. MRP14, another S100 protein generally coordinately expressed with human MRP8, was not induced by LPS under the same conditions. We propose that CP-10 may play a key role in recruitment of leukocytes into tissues in response to gram-negative bacterial infection.

Animals

Retinoblastoma in association with the chromosome breakage syndromes Fanconi's anaemia and Bloom's syndrome: clinical and cytogenetic findings.

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin-C-induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X-ray-induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid-type aberrations. She had a number of typical clinical features, including cafe-au-lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelodysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin-C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous 'butterfly rash' Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

Bloom Syndrome

Preliminary results from a psychoeducational program to rehabilitate chronic patients.

Twenty-two chronic psychiatric patients enrolled in a psychoeducational rehabilitation program were assessed before and after the program to determine whether participation decreased severity of psychopathology and improved community functioning and quality of life. The program consisted of five 14-week modules that provided training in five skill areas: medication and symptom self-management, coping with anxiety and depression, social skills, living skills, and leisure skills. Most patients experienced significantly reduced psychopathology and negative symptoms and improved quality of life and community functioning. The program appears helpful to clients, and a controlled trial to further evaluate its effects is underway.

Activities of Daily Living

Strecker stents in the femoropopliteal arteries: value of duplex ultrasonography in restenosis assessment.

PURPOSE: Experience with Strecker stent implantation in the femoropopliteal arteries has been described; however, few of the reports were prospective studies, and none routinely used site-specific assessment methods for follow-up evaluation of stent patency. The purpose of this study was to evaluate 1-year Strecker stent patency using duplex ultrasound imaging to obtain a more precise delineation of stent restenosis than is possible with other noninvasive assessment modalities. METHODS: A prospective study involved 52 patients with 57 sites treated by angioplasty and Strecker stent deployment in the femoropopliteal arteries. Assessment included clinical evaluation; ankle-brachial index (ABI) measurements at rest and after exercise; and duplex ultrasound imaging preprocedurally and at 3 and 12 months after the intervention. RESULTS: All 74 stents were deployed successfully in the 35 occluded arteries and 22 stenotic lesions. Acute reocclusion occurred in 6 (10%). At 3 months, primary patency was 81% and secondary patency 84%. Mean ( +/- SD) ABIs increased from 0.64 +/- 0.15 at rest and 0.32 +/- 0.17 after exercise to 0.89 +/- 0.14 and 0.68 +/- 0.23, respectively (p < 0.0001). At 12 months, primary patency was 79%, and secondary patency was 82%. Mean ABIs were 0.82 +/- 0.15 at rest and 0.52 +/- 0.22 after exercise at 12 months (p < 0.0002 compared with preprocedural ABIs). Analysis of the length of lesion treated showed betted results with shorter diseased segments, but this was not statistically significant (p > 0.05). Better outcomes were also obtained when one stent was used rather than two stents at 12 months (p = 0.15), but there was no difference at 3 months (p = 0.3). Thirty-four percent of the stented segments progressed from < 20% stenosis at 3 months to > 50% stenosis at 12 months. Overall, 19 (43%) of 44 segments progressed from < 50% stenosis at 3 months to a > 50% stenosis at 12 months. Restenosis seen at 3 months generally was in the native artery just proximal or distal to the stent, but at 12 months, restenosis was mainly inside the stent. CONCLUSIONS: Strecker stents at 1-year demonstrated satisfactory patency in the femoropopliteal arteries when deployed for angioplasty salvage or recurrent disease. The 3- and 12-month evaluations obtained with duplex ultrasound provided site-specific hemodynamic data for stent assessment. Resting ankle pressures were a poor index of restenosis.

Aged

Identification of an abundant disulfide-linked complex of glycoproteins in the envelope of guinea pig cytomegalovirus.

Murine monoclonal antibodies were used to identify an immunogenic envelope glycoprotein complex of guinea pig cytomegalovirus (GPCMV). The glycoprotein complex consisted of two virion components of estimated masses 60,000 and 90,000 Da. Murine monoclonal antibodies specific for the gp60-90 complex neutralized infectious virus in the presence of complement and detected expression of the envelope complex on the surface of infected cells. Pulse-chase and immunoblot analyses suggested that these virion forms were proteolytic products of an intracellular polyprotein precursor of an estimated molecular weight of 150,000 Da (gp150). In addition, the intracellular forms of this envelope glycoprotein complex existed as a disulfide-linked oligomer. The intracellular polyprotein was synthesized as a 100,000-Da precursor which was likely cotranslationally glycosylated using N-linked linkages to the major intracellular form, gp150. Because of the similarities in size, expression, and processing pathway, these results suggested that the GPCMV gp60-90 complex may represent the HCMV gB homolog of GPCMV.

Animals

Endotracheal tube and tracheobronchial obstruction as causes of hypoventilation with high inspiratory pressures.

Two cases of difficult ventilation are presented, the first caused by endotracheal tube obstruction with nasal turbinate, and the second caused by tracheobronchial obstruction with blood clots. The clinical presentation in each case was characterized by extreme difficulty in ventilating and severe hypercapnia despite vigorous ventilatory efforts with either a mechanical ventilator or resuscitator bag. A simple manipulation of the endotracheal tube cuff helped to differentiate between increased impedance caused by endotracheal tube obstruction as opposed to increased respiratory system impedance beyond the tip of tube. In the second patient, in whom even a short interruption of ventilation was poorly tolerated, simultaneous rigid bronchoscopy (for removal of intratracheal masses) and ventilation via endotracheal tube were successfully performed.

Adult