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Biomedical subjects

S M Mitchell

Publications and source records attributed to S M Mitchell.

At least 37 records · Page 2Linked to original sources

Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors.

OBJECTIVE: To assess the effect of combination antiretroviral therapy including HIV protease inhibitors on the survival of patients with cytomegalovirus retinitis (CMVR). DESIGN AND PARTICIPANTS: A longitudinal study of patients with CMVR diagnosed between October 1992 and May 1996 and followed to May 1997. SETTING: UK National Health Service specialist HIV medicine department. OUTCOME MEASURE: Time to death from first diagnosis of CMVR. Data were censored on 31 May 1997. RESULTS: Data were available on 147 patients with CMVR. Median survival of CMVR patients before December 1995 was 256 days [95% confidence interval (CI), 197-315]. Following the introduction of protease inhibitors in December 1995 this rose to 555 days (95% CI, 351-759). By 31 May 1996 median survival for the entire group of patients alive with CMVR had risen to 720 days (95% CI, 551-889). The mean survival after CMVR diagnosis was 224 days (n=89; 95% CI, 186-261; 1-year survival, 16%) in those who took no further antiretroviral therapy, 353 days in those who took nucleoside reverse transcriptase inhibitors but no protease inhibitors (n=34; 95% CI, 289-418; 1 -year survival, 50%), and 914 days in those who took a protease inhibitor (n=24; 95% CI, 768-1059; 1-year survival, 83%; P < 0.0001). Multivariate analysis showed that the strongest independent predictor of improved survival was having ever received a protease inhibitor after CMVR (relative risk of death, 0.063; 95% CI, 0.027-0.149; P < 0.0001). CONCLUSIONS: The use of HIV protease inhibitors in combination antiretroviral therapy has been associated with a marked increase in the survival of patients with CMVR.

AIDS-Related Opportunistic Infections↗

Intraocular inflammation and the diffuse infiltrative lymphocytosis syndrome.

PURPOSE: To report a case of bilateral panuveitis associated with diffuse infiltrative lymphocytosis syndrome (DILS). METHODS: Case report. A 35-year-old woman with known human immunodeficiency virus (HIV) infection developed bilateral uveitis with retinal periphlebitis in association with diffuse infiltrative lymphocytosis syndrome. RESULTS: Detailed comprehensive examination and investigations were performed and recognized causes of panuveitis excluded. CONCLUSION: To the best of our knowledge, we report the first case of retinal findings associated with diffuse infiltrative lymphocytosis syndrome.

Adult↗

Aqueous and vitreous humor samples for the diagnosis of cytomegalovirus retinitis.

PURPOSE/METHODS: Techniques for detection of viral DNA based on the polymerase chain reaction are increasingly being applied to ocular fluids; however, the clinical significance of such findings can sometimes be unclear. Two patients had the acquired immunodeficiency syndrome (AIDS) in whom different herpesviruses were detected in aqueous and vitreous fluids from the involved eye. RESULTS/CONCLUSIONS: In both patients dual viral infections were present and the application of polymerase chain reaction-based methods to ocular fluids made a useful contribution to the treatment of the patients.

AIDS-Related Opportunistic Infections↗

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

AIDS-Related Opportunistic Infections↗

Retinal detachment and herpesvirus retinitis in patients with AIDS.

BACKGROUND: The prolongation of survival of patients with herpesvirus retinitis and AIDS has been associated with a rise in the incidence of retinal detachment. In such cases, however, retinal reattachment may be difficult to achieve, and postoperative visual acuity may be poor despite anatomically successful surgery. METHODS: In order to examine factors affecting the visual outcome of surgery, a retrospective review of 29 patients with retinal detachment, herpesvirus retinitis, and AIDS was performed. Retinal reattachment surgery (32 procedures) or prophylactic laser demarcation (five procedures) was performed in 28 eyes of 23 patients. RESULTS: The macula was attached in 23/28 (82%) eyes at the last outpatient visit. Best postoperative visual acuity (median 6/18, range 6/6-hand movements) was significantly greater than final postoperative acuity (median counting fingers, range 6/6-no perception of light) (Wilcoxon sign rank test, p = 0.003), and was retained for a median of 3 months (1-91 weeks) after surgery. Poor visual outcome as evidenced by submedian final visual acuity was invariably associated with persistence of macular detachment, and significantly associated with the occurrence of optic atrophy (odds ratio = 5, p = 0.02). CONCLUSION: Retinal reattachment surgery appears justified in patients with herpesvirus retinitis and AIDS, but postoperative visual deterioration may occur in association with optic atrophy.

AIDS-Related Opportunistic Infections↗

Inhibition of platelet heparitinase by phosphorothioate DNA oligonucleotides.

In view of the role that heparitinase and heparanase enzymes are thought to play in regulating the proliferation of smooth muscle cells, inhibitors of these enzymes may have therapeutic value in the treatment of vascular hyperplasia. Here we report that phosphorothioate oligodeoxynucleotides inhibit platelet heparitinase and related enzymes in vitro. The inhibition is greatly enhanced by the presence of a GGG motif in the oligonucleotide, and also increases with oligonucleotide for two phosphorothioate DNA 30-mers consisting solely of guanosine and thymidine nucleotides. Their inhibitory efficacy was greater when heparan sulphate was used as substrate.

Base Sequence↗

Vitreous fluid sampling and viral genome detection for the diagnosis of viral retinitis in patients with AIDS.

Cytomegalovirus (CMV) causes severe necrotizing retinitis in patients with the acquired immune deficiency syndrome (AIDS) and other herpesviruses have been implicated in the acute retinal necrosis syndrome (ARN), seen in both the immunocompetent and the immunosuppressed. At present the diagnosis of viral retinitis relies solely on clinical appearances. In order to assess whether the detection of herpesvirus-specific DNA in cell-free vitreous biopsy samples could be useful in the early diagnosis of viral retinitis, vitreous fluid samples were taken from 100 patients. Fifty patients had AIDS as defined by the Centers for Disease Control, (MMWR 36 (suppl 1S):1S-15S, 1987) and retinal disease. The remainder were not known to be HIV infected and had no clinical evidence of retinal infection. Each sample was tested for the presence of CMV, herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV6), by amplification of viral DNA using a sensitive and specific nested polymerase chain reaction (PCR). The presence of detectable CMV or VZV DNA was clearly associated with clinical disease whereas the presence of HSV-1, EBV, and HHV6 sequences were not. Clinical discrimination between CMV- and VZV-associated retinitis was greatly enhanced when the PCR results were taken into consideration.

AIDS-Related Opportunistic Infections↗

Detection of varicella-zoster virus DNA in ocular samples from patients with uveitis but no cutaneous eruption.

Herpes zoster ophthalmicus is a well-recognised cause of intraocular inflammation, which may become recurrent or chronic after the acute phase has elapsed. Although it commonly presents with the typical rash, cases of ocular zoster with no cutaneous eruption have been well documented. We present two patients with unilateral anterior uveitis complicated by cataract, in whom molecular techniques based on the polymerase chain reaction detected varicella-zoster virus DNA in intraocular material obtained during cataract surgery. Neither patient gave a history of cutaneous eruption.

Cataract↗

Corneal endothelial changes in cytomegalovirus retinitis.

Reticular deposits on the corneal endothelium together with fundus changes typical of cytomegalovirus (CMV) retinitis have been noted in patients with acquired immune deficiency syndrome (AIDS). The aim of this study was to characterise this finding using specular microscopy and to assess the potential of this clinical sign as a screening tool which could be performed rapidly at the slit lamp without the need for dilatation of the pupil. Sixty male homosexual patients with a diagnosis of AIDS as defined by the Center for Disease Control (Atlanta, 1987) were examined at their first visit to the ophthalmic clinic. The cornea was examined at the slit lamp prior to fundal examination and the presence or absence of the characteristic endothelial changes noted. CMV retinitis was diagnosed on the basis of the fundal appearance together with confirmation of the diagnosis by analysis of a vitreous sample. As a diagnostic sign of CMV retinitis the endothelial changes had a positive predictive value of 94.7% and a negative predictive value of 75.6%. Although the presence of the endothelial changes always indicates the presence of CMV retinitis it is not a sign which is found in a high enough proportion of patients to allow its reliable use as a screening tool.

Acquired Immunodeficiency Syndrome↗

Case study in perioperative right heart failure.

Today, we are increasingly aware of the important role the right ventricle plays in maintaining hemodynamic stability. When the right ventricle fails, added stress is placed on the cardiovascular system. This article focuses on patients with perioperative right heart failure and the associated complex nursing care that is needed to manage these patients. Three major nursing diagnoses are reviewed, including decreased cardiac output, impaired gas exchange, and high risk for ineffective family coping.

Aged↗

Evaluation of zinc salt based fixatives for preserving antigenic determinants for immunohistochemical demonstration of murine immune system cell markers.

Conventional aldehyde based fixatives produce good morphological preservation. However, owing to their cross-linking mechanism of action, epitope loss may occur during fixation compromising the tissue for subsequent immunohistochemical (IHC) analysis. IHC is an important tool for characterizing antigen, cytokine and cytomorphological markers. The increasing use of mouse models for study of pathogenesis has highlighted the need to investigate alternative fixatives. In the study reported here, tissue samples from RIII mice with immune mediated lesions, Mycobacterium bovis infected mice, and uninfected control mice were fixed in either zinc salt fixative or buffered formalin, then tested for IHC using a panel of antibodies (CD3, CD4, CD8, CD45, CD54, F4/80, Interferon-gamma and MIP2). Zinc salt fixation preserved processing-sensitive murine cell markers (CD4, CD8 and CD54) and improved the intensity of immunolabeling for CD45, F4/80 and CD3. Buffered formalin failed to preserve any of the processing-sensitive murine epitopes for demonstration by subsequent IHC.

Animals↗