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Biomedical subjects

M R Nelson

Publications and source records attributed to M R Nelson.

At least 91 records · Page 5Linked to original sources

Treatment with corticosteroids--a risk factor for the development of clinical cytomegalovirus disease in AIDS.

OBJECTIVE: To assess the frequency with which HIV-seropositive patients treated with corticosteroids develop cytomegalovirus (CMV) disease. DESIGN: Retrospective case-controlled study. METHODS: All 130 patients receiving systemic corticosteroids over a 20-month period at the HIV Unit, Westminster Hospital, London, UK were reviewed for the development of clinical CMV disease within 28 days. The incidence of CMV disease in this group was compared with that in a cohort admitted during the same period, which was matched for admission diagnosis, HIV risk group, antiretroviral therapy and CD4 lymphocyte subset count (+/- 20%) at admission. RESULTS: Eleven of the 130 patients given corticosteroids developed CMV disease within 28 days, compared with two patients in the case-controlled cohort. All patients who developed CMV disease had a CD4 count < 50 x 10(6)/l on admission. CONCLUSION: The use of corticosteroids in patients with advanced immunosuppression due to HIV infection should be reviewed carefully in view of the possible increased incidence of CMV disease.

AIDS-Related Opportunistic Infections↗

The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)

One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.

AIDS-Related Complex↗

Salmonella, Campylobacter and Shigella in HIV-seropositive patients.

OBJECTIVE: To study the incidence, clinical features, treatment and outcome of patients with Salmonella, Shigella or Campylobacter infection. DESIGN: Retrospective analysis. SETTING: Two dedicated HIV units within a London teaching hospital. METHODS: All patients with Salmonella, Shigella or Campylobacter infection were reviewed retrospectively by correlating the records of the gastrointestinal and microbiology departments with the computerized records of all HIV-positive patients attending the two clinics. RESULTS: Between July 1985 and June 1991, 56 episodes of Salmonella, 37 of Campylobacter and eight of Shigella infection were documented in HIV-seropositive patients. Shigella was most likely to occur early in HIV disease, whilst patients with Campylobacter or Salmonella were more likely to have had a previous AIDS diagnosis. Septicaemica was most common in patients with Salmonella and was especially likely to occur in individuals with an AIDS diagnosis. Relapse of infection was common in patients with Salmonella, especially in those with low CD4 lymphocyte counts, those with an initial septicaemic illness and those not treated with ciprofloxacin. CONCLUSIONS: Patients with Salmonella who have low CD4 lymphocytes counts and/or a septicaemic illness should be considered for life-long secondary prophylaxis with ciprofloxacin because of the high rate of relapse observed. Administration of zidovudine or cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia may prevent the development of salmonellosis: significantly fewer patients with this infection were taking these drugs than patients with Campylobacter.

AIDS-Related Opportunistic Infections↗

Effects of the expression of mammalian annexins in yeast secretory mutants.

The hypothesis that calcium-dependent membrane-binding proteins of the annexin family can influence intracellular membrane trafficking was tested by expressing five mammalian annexins in wild-type yeast cells (Saccharomyces cerevisiae) and in 13 yeast secretory (sec) mutants. Expression of human synexin (annexin VII) inhibited the growth of sec2, sec4 and sec15 mutants at a semi-permissive temperature. These three sec mutants are defective in the final step in the secretory pathway, the process of exocytosis. The inhibition of growth correlated with reduced viability and increased accumulation of internal invertase in these mutants when expressing synexin. Bovine endonexin (annexin IV) partially suppressed the growth defect of a sec2 mutant incubated at a semi-permissive temperature. Human synexin, human lipocortin (annexin I), and murine p68 (annexin VI) reduced the lag time associated with adaptation of sec2 mutants to galactose-containing medium. These interactions suggest that the annexins may influence specific steps in membrane trafficking associated with cell growth, secretion and plasma membrane remodelling.

Annexins↗

Pseudomonas septicaemia associated with HIV.

Between July 1985 and January 1990, pseudomonas scepticaemia occurred in 19 out of 584 patients with AIDS attending the Westminster and St Stephen's AIDS Unit, London, UK. Ten of these 19 were being treated for active cytomegalovirus infection. Fourteen of the 19 patients had a central venous catheter in situ, which was the source of infection in 11. Seven patients died. Mortality was significantly greater in those patients infected with Pseudomonas aeruginosa, in those patients whose source of infection was not the central venous line, and in those patients whose central line was not removed.

Acquired Immunodeficiency Syndrome↗

Foscarnet in the treatment of cytomegalovirus infection of the esophagus and colon in patients with the acquired immune deficiency syndrome.

Foscarnet, administered via a central line, was used for the treatment of 18 episodes of cytomegalovirus (CMV) esophageal ulceration in 15 patients, and in the treatment of 27 episodes of CMV colitis in 22 patients. In 15 of the 18 episodes of the esophageal disease, there was complete loss of symptoms within 2 wk. Only three of the 15 patients responding to foscarnet therapy had a relapse of their esophageal disease. Two of these patients were successfully retreated with foscarnet. Of the 22 patients receiving foscarnet for CMV colitis, four died during foscarnet therapy. Of the 18 patients completing the course of treatment with foscarnet for first-episode CMV colitis, 11 remitted completely and six had a partial remission. All patients with partial remission had a second pathogen responsible for the continuation of their diarrhea. Only one patient completing a course of foscarnet failed to respond microscopically to treatment. Three patients experienced relapse of their CMV colitis, two of whom responded to further courses of foscarnet. Foscarnet is an effective therapy for CMV disease of the gastrointestinal tract, with rapid resolution of clinical symptoms, long-term remission of esophageal disease, and shorter disease-free periods for CMV colitis.

Acquired Immunodeficiency Syndrome↗

The value of serum cryptococcal antigen in the diagnosis of cryptococcal infection in patients infected with the human immunodeficiency virus.

Serum cryptococcal antigen titres were measured in 828 HIV-infected patients with pyrexia, 69 of whom had meningism. Serum cryptococcal antigen was positive in 17 patients of whom 16 had meningism with cryptococcus isolated from their CSF. The other patient had no meningism, had no evidence of cryptococcal infection on repeated CSF examination and remains well. A positive serum cryptococcal antigen test was therefore valuable in the diagnosis of cryptococcal meningitis, although in all 16 patients meningism was present and a diagnostic lumbar puncture was therefore carried out. In our experience routine screening for serum cryptococcal antigen did not predict patients who subsequently developed cryptococcal meningitis.

Amphotericin B↗

The significance of the detection of cytomegalovirus in the bronchoalveolar lavage fluid in AIDS patients with pneumonia.

We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bronchoscopy and in whom Pneumocystis carinii pneumonia (PCP) and/or cytomegalovirus (CMV) were identified in bronchoalveolar fluid (BAL). CMV was identified by detection of early antigen fluorescent foci (DEAFF) testing in cell cultures of BAL fluid. The short- and long-term survival of all patients was similar regardless of whether PCP, CMV or both were detected at bronchoscopy. Ten out of 14 patients with CMV alone and 13 out of 26 with both CMV and PCP were treated with anti-CMV therapy, but the short- and long-term mortality was similar to that in patients who had no specific antiviral therapy. Extrapulmonary recurrence of CMV (retinitis or gastrointestinal disease) occurred in 22% of patients with evidence of CMV in BAL compared with 16% of those with PCP alone, but this difference was not statistically significant and this recurrence rate was independent of anti-CMV therapy. Detection of CMV shedding from more than one site (BAL, urine, throat or blood) was associated with a worse prognosis at 3 months than in patients in whom CMV was detected in BAL alone. It does not appear that finding CMV shedding is a guide to the cause of pneumonia or an indication for treatment in AIDS patients.

Acquired Immunodeficiency Syndrome↗

The present and the future of AIDS and tuberculosis in Illinois.

The relation between the acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) was examined by matching the Illinois AIDS and TB registries. The match group was examined and compared with patients with only one disease by race, method of human immunodeficiency virus (HIV) transmission, site of tuberculous disease, radiographic findings, and results of Mantoux tests. The time of TB diagnosis was centrally distributed around the time of AIDS diagnosis; from this, it was determined that 4.1 percent of AIDS patients develop active TB. Projections for future AIDS cases were made by fitting a polynomial model to historical data. These projections were then used to predict the future impact of AIDS-related TB upon state TB rates. The rise in TB rates call for special efforts to minimize this impact.

Acquired Immunodeficiency Syndrome↗

The discrimination of similarly colored objects in computer images of the ocular fundus.

The STARE (STructured Analysis of the REtina) project uses object-identification and artificial intelligence techniques to provide automated diagnoses from color pictures and fluorescein angiograms of the ocular fundus, or automated change detection from sequential images. As part of the object-identification process, we apply expert judgment and experimentation to define features--such as size, shape, color, and texture--of objects (disk, blood vessels, lesions) in digitized images. In our initial investigations, we explored color alone, because it yields a great deal of information in the classification process. We verified that even similarly colored lesions (exudates, cotton-wool spots, and drusen) could be classified by color with moderate success by a quadratic discriminant function. When color alone is not sufficient, refinement in the classification of objects may be achieved by using more features in statistical pattern recognition. Ultimately, we build a description of the fundus image which can be used either to identify one or more diagnoses that can cause the pattern of lesions in the ocular fundus or to recognize change in sequential images.

Color↗

Posterior femoral cutaneous nerve conduction.

The posterior femoral cutaneous nerve is a sensory nerve comprised of fibers originating from the anterior and posterior divisions of the first three sacral segments. It exists the pelvis distal to the piriformis muscle and proceeds distally, superficial to and between the medial and lateral hamstring musculature. The nerve's major cutaneous distribution is the posterior aspect of the thigh and a variable area of the posterior calf. An electrophysiologic technique to assess the peripheral axons of the posterior femoral cutaneous nerve is described. A recording electrode is placed 6cm proximal to the midpopliteal fossa and the nerve is stimulated supramaximally 12cm proximally on a line between the active electrode and the ischial tuberosity. A ground electrode is placed just proximal to the active recording electrode. The lower extremities of 40 individuals with a mean age of 34 years (20 to 78 years) were examined. The mean peak latency of the response is 2.8 (2.3 to 3.4) msec +/- 0.2msec with a mean amplitude of 6.5 (4.1 to 12.0) microV +/- 1.5 microV. This technique may facilitate the proximal evaluation of lower extremity peripheral neuropathies, lesions of the posterior femoral cutaneous nerve, or the assessment of the peripheral nervous system in persons with lower extremity amputations.

Action Potentials↗

Guillain-Barré syndrome in children: evidence of axonal degeneration and long-term follow-up.

A retrospective study was done of 12 children who met the NINCDS clinical criteria for the diagnosis of Guillain-Barré syndrome and who were hospitalized with this diagnosis. Electrodiagnostic testing was sufficiently complete for interpretation of the neuropathophysiology in six children. Long-term outcome was determined through examination by a physician one to eight years after onset in all six children, and was supplemented by telephone follow-up with the children or their parents by the authors five to eight years after onset. Long-term clinical outcome was analyzed for any correlation between poor outcome and axonal degeneration. The electrodiagnostic tests were consistent with primarily axonal neuropathophysiology in three of the six children. Poor clinical outcome appeared to correlate with electrodiagnostic evidence of primarily axonal pathophysiology, or absence of an evoked M-response, or both.

Adolescent↗