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Biomedical subjects

C Pedersen

Publications and source records attributed to C Pedersen.

At least 73 records · Page 4Linked to original sources

T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters.

Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because of a relatively low number of CD4 lymphocytes. Primary infection was followed by prolonged and severe cellular hyporesponsiveness to both mitogens and antigen. At the last follow-up, responses to pokeweed mitogen were still severely impaired, with a median 19% (range 7-50%) of that observed in healthy controls. We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio.

Adult

Trends in survival of Danish AIDS patients from 1981 to 1989.

Length of survival was analysed in relation to year of diagnosis, AIDS-indicative disease, age, risk behaviour, zidovudine therapy, and CD4 cell count and serum immunoglobulin (Ig) levels at the time of diagnosis in a group of 231 consecutive adult Danish AIDS patients reported before 1 January 1988. The cumulative survival rate was 53% (95% confidence interval 47-59%) at 1 year, 29% (22-36%) at 2 years and 18% (10-26%) at 3 years. Length of survival increased significantly (P less than 0.001) over time for patients who were initially diagnosed with Pneumocystis carinii pneumonia (PCP), 17% (3-31%) at 2 years prior to 1986, 32% (16-49%) in 1986 and 52% (34-69%) in 1987, whereas survival remained stable for patients with other AIDS-indicative diseases. Survival was similar for patients who were diagnosed with Kaposi's sarcoma alone and PCP alone. Independent predictors of a shortened survival were a CD4 cell count less than 200 x 10(6)/l, a serum IgA level greater than 4 g/l, and an initial diagnosis with opportunistic infections other than PCP. In addition, the multivariate analysis suggested an improved survival in recent years for patients diagnosed with PCP, independent of other factors examined. We conclude that length of survival in AIDS patients is highly variable. Determinants of progression include CD4 cell count, serum IgA level, and presenting disease. Survival has increased markedly for patients with PCP and median survival now exceeds 24 months.

Acquired Immunodeficiency Syndrome

Reactivation of viral replication in anti-HBe positive chronic HBsAg carriers.

Reactivation of hepatitis B virus replication was investigated in an unselected group of 44 HBV DNA negative, anti-HBe positive chronic HBsAg carriers. Twenty-five patients (54%) were intravenous drug addicts and 7 (16%) were male homosexuals. Sixteen patients had evidence of delta infection and five of the seven male homosexuals had human immunodeficiency virus infection. The patients were followed for 1 to 180 months (median, 24 months) while HBV DNA negative, anti-HBe positive. Reactivation, defined as reappearance of HBV DNA or HBeAg, or both, was detected in six patients corresponding to an annual reactivation rate of 5%. Reactivation in four patients was detected by reversion to HBV DNA positivity only, whereas HBeAg/anti-HBe status remained unchanged. Two patients became both HBV DNA and HBeAg positive. None of the patients developed hepatitis-like symptoms and transaminase elevation was only observed in two patients. Reactivation in two patients was ascribed to human immunodeficiency virus infection and in one patient to chronic lymphatic leukaemia. It is concluded that HBV DNA seems to be superior to HBeAg in the detection of reactivation of HBV replication and that reactivation associated with clinical symptoms leading to progression in chronic liver disease is a rare event in the population studied.

Adolescent

Subclinical hypothyroidism: a review of neuropsychiatric aspects.

The authors review current information about the prevalence, causes, course, and consequences of subclinical hypothyroidism. There is evidence that subclinical hypothyroidism may be associated with cognitive dysfunction, mood disturbance, and diminished response to standard psychiatric treatments. Recommendations are presented for the screening, evaluation and treatment of patients in whom subclinical hypothyroidism may be contributing to neuropsychiatric dysfunction.

Humans

Echocardiographic screening in 24 consecutive AIDS patients.

To assess the prevalence and extent of cardiac abnormalities in patients with newly diagnosed AIDS, 24 consecutive patients admitted for treatment for acute opportunistic infections were examined with echocardiography during hospitalisation. None of the patients had known cardiac disease or were drug abusers. A total of 16 abnormalities were identified in 13 patients (54%). Nine patients had a right ventricular diameter exceeding 26 mm, two patients had a slightly dilated left atrium or left ventricle, respectively, and five had a moderate pericardial effusion (range 2-8 mm). Left ventricular contractility was normal in all patients. Survival rates between AIDS patients with or without cardiac abnormalities were identical. It is concluded that minor cardiac abnormalities are common in AIDS patients with acute opportunistic infection. However, echocardiography in this group of AIDS patients without cardiac complaints gives no important functional or prognostic information as a routine procedure.

Acquired Immunodeficiency Syndrome

Polymorphous low grade adenocarcinoma of minor salivary gland: a clinicopathologic and comparative immunohistochemical study.

Retrospective review of seven cases of polymorphous low grade adenocarcinoma (PLGA) revealed that the original histologic diagnosis in five instances was mixed tumor (four benign and one malignant). Comparison of PLGA tumors with eleven representative cases of benign pleomorphic adenoma of minor salivary gland (BPA) showed marked similarity in cytologic features. PLGA and BPA also exhibited similar mucohyaline and/or fibromyxoid stromal components. In contrast, tumor margins of the two neoplasms were quite different; margins of PLGA were consistently infiltrative, whereas those of BPA were generally well circumscribed and encapsulated. Immunophenotypic comparison confirmed the glial fibrillary acidic protein (GFAP) positivity in BPA reported by others, whereas cases of PLGA were uniformly nonreactive with this antibody. Although previous reports have emphasized the histologic similarities of PLGA and adenoid cystic carcinoma, our findings indicate that differentiation of PLGA from BPA may represent a more common diagnostic problem. Awareness of comparative histologic features is important in the differential diagnosis of these minor salivary gland neoplasms. Also, monoclonal GFAP may be useful in distinguishing cases of PLGA from BPA where histologic features are otherwise similar.

Adenocarcinoma

Clinical course of primary HIV infection: consequences for subsequent course of infection.

OBJECTIVE: To investigate the impact of the clinical course of the primary HIV infection on the subsequent course of the infection. DESIGN: Prospective documenting of seroconversion, follow up at six month intervals, and analysis of disease progression by life tables. PATIENTS: 86 Men in whom seroconversion occurred within 12 months. PRIMARY OUTCOME MEASURE: Progression of HIV infection, defined as CD4 lymphocyte count less than 0.5 X 10(9)/l, recurrence of HIV antigenaemia, or progression to Centers for Disease Control group IV. MAIN RESULTS: Median follow up was 670 (range 45-1506) days. An acute illness like glandular fever occurred in 46 (53%) subjects. Three year progression rates to Centers for Disease Control group IV was 78% at three years for those who had longlasting illnesses (duration greater than or equal to 14 days) during seroconversion as compared with 10% for those who were free of symptoms or had mild illness. All six patients who developed AIDS had had longlasting primary illnesses. Three year progression rates to a CD4 lymphocyte count less than 0.5 X 10(9)/l and to recurrence of HIV antigenaemia were significantly higher for those who had longlasting primary illnesses than those who had no symptoms or mild illness (75% v 42% and 55% v 14%, respectively). CONCLUSION: The course of primary infection may determine the subsequent course of the infection.

Acquired Immunodeficiency Syndrome

HIV-induced immunodeficiency. Relatively preserved phytohemagglutinin as opposed to decreased pokeweed mitogen responses may be due to possibly preserved responses via CD2/phytohemagglutinin pathway.

We studied the proliferative response of PBL to the mitogens PHA and PWM and Candida albicans Ag in 301 HIV seropositive homosexual men, of whom 55 had AIDS. The responses to PHA were reduced only in the clinically ill HIV seropositive subjects. In contrast, the responses to PWM were profoundly reduced in most HIV seropositive subjects including the asymptomatic group. Further analysis of 16 HIV seropositive subjects showed that the proliferative responses were reduced in both CD4 and CD8 T cell subsets. A total of 15 HIV seropositive individuals with low responses to PWM, of whom seven had AIDS and eight controls were chosen for the following studies. Expression of T3, Ti, delta receptors, and CD2 was investigated and showed an increased percentage of CD2 receptors positive cells in HIV seropositive subjects without AIDS. The proliferative responses of PBL to stimulation with PHA, PWM, antibodies to CD3, or antibodies to CD2 were investigated and showed significant correlation in controls, whereas in contrast, only the responses to PHA and CD2ab correlated in patients with AIDS. The proliferative responses to CD2ab and CD3ab in controls were larger than the responses to both PHA and PWM. In patients, these responses were less suppressed than the responses to PWM indicating that stimulation with mitogens is more complex than a simple stimulation of Ti/T3 and CD2 receptors. Further investigations were done on resting T cells, i.e., lymphocytes depleted of macrophages and pre-activated cells. Addition of PHA to these cells resulted in preactivation with expression of IL-2R (CD25) but not in proliferation. In contrast, addition of PHA plus SRBC, which bind to the CD2 receptors caused IL-2R expression, IL-2 production, and proliferation. Addition of PWM + SRBC did not result in proliferation. A comparison of the responses to PHA + SRBC of resting T cells from 26 HIV seropositive individuals, of whom seven had AIDS and 12 seronegative controls, showed that these responses were normal or only slightly decreased in the 19 seropositive men without AIDS whereas it was decreased in AIDS patients. Nevertheless, all AIDS patients showed clear-cut responses in this assay. Thus, the discrepancy between responses to PHA and PWM may be explained by an at least partially preserved function of the PHA/CD2-dependent pathway. We suggest that the defect induced by the HIV infection primarily concerns T3/Ti-induced responses.

Acquired Immunodeficiency Syndrome

Isolation of HIV using T-lymphocyte 'panning': methodological aspects.

A technique for isolation of HIV using selective cultures of T4 cells obtained from peripheral blood by immunochemical separation was developed and optimized. Using this method infectious virus could be isolated in single isolation attempts from 89% of 35 HIV-infected patients in different stages of immunodeficiency. This isolation frequency was virtually independent of the stage of the disease, in contrast to the results obtained by the conventional isolation technique based on peripheral mononuclear cells (PMC). It is concluded that isolation of HIV from selected T4 cells is superior to other methods when isolation is attempted from healthy HIV-infected individuals.

Antibodies, Monoclonal

Suppression of p24 antigen in sera from HIV-infected individuals with low-dose alpha-interferon and zidovudine: a pilot study.

On the basis of the observations that HIV antigenaemia indicates a high risk of progression to AIDS and that zidovudine and alpha-interferon act synergistically against HIV replication in vitro, we performed a pilot trial including 12 HIV-infected asymptomatic patients with detectable p24 antigen in serum. The patients received low-dose lymphoblastoid alpha-interferon alone for 4 weeks followed by a combination of interferon and low-dose zidovudine for a further 16 weeks. The median p24 antigen level decreased significantly (P less than 0.01), the decrease being most pronounced at week 5. Decreases in haemoglobin and neutrophil counts were observed. Four patients required reduction of the zidovudine dose and three patients were transfused. In conclusion, the drug combination was capable of reducing the serum level of HIV p24 antigen and it was tolerated by the patients. Further studies are required to evaluate the clinical implications of these observations.

Acquired Immunodeficiency Syndrome

Serum thymidine kinase--a marker of bone marrow toxicity during treatment with zidovudine.

Serum thymidine kinase (S-TK) was measured weekly in 16 randomly selected patients with AIDS or AIDS-related complex (ARC; Centers for Disease Control group IV A or group IV C-2) who participated in a controlled study of the efficacy of zidovudine therapy. S-TK increased significantly (P less than 0.01) in the zidovudine group, whereas it remained stable in the placebo (control) group. On the basis of this observation, the value of S-TK measurements as a predictor of bone marrow toxicity during zidovudine therapy was investigated in 42 patients with AIDS or ARC who received zidovudine as part of their usual treatment. There was a significant association between S-TK, haemoglobin and neutrophil counts measured after the first 4 weeks of therapy and the risk of developing bone marrow toxicity during the following 6 months. Combined, measurements of S-TK and neutrophil counts seem to be well suited for the identification of patients who have a high probability for developing bone marrow toxicity during zidovudine treatment.

AIDS-Related Complex

The development of AIDS or AIDS-related conditions in a cohort of HIV antibody-positive homosexual men during a 3-year follow-up period.

One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes less than 0.5 x 10(9) l-1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes less than 0.3 x 10 l-1 and elevated serum level of IgA were significantly associated with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy. When adjusted to the probable year of infection, these results are in accordance with previous cohort studies. It is concluded that most, or all, subjects seropositive for HIV will develop progressive loss of CD4 lymphocytes followed by clinical signs of immune deficiency, and that differences among previous cohorts with respect to disease progression are probably due to differences in the duration of infection.

AIDS-Related Complex

Benzodiazepine antagonism by aminophylline.

A double-blind, randomised study was performed to investigate whether aminophylline could reverse the sedative effect of benzodiazepine and if it could shorten the observation time necessary after benzodiazepine sedation. Forty patients undergoing minor abdominal, urogenital or lower extremity surgery were given benzodiazepine to maintain a state of deep sedation after spinal or epidural analgesia was achieved. Postoperatively, the patients received either aminophylline, 110 mg, or physiological saline intravenously. The aminophylline-treated patients showed a significantly more rapid reversal of sedation, but after 30 min there was no difference between the two groups. It is concluded that aminophylline antagonizes the sedative effect of benzodiazepine, but in routine benzodiazepine sedation, aminophylline will not shorten the necessary observation period after sedation.

Adult

Tubuloreticular inclusions in skin biopsies from patients with HIV infection.

Skin biopsies obtained from apparently normal skin from 15 HIV infected patients and 6 anti-HIV negative patients were examined by electron microscopy. Tubuloreticular inclusions (TRI) were detected within the cytoplasm of capillary endothelial cells in 5/5 AIDS patients and in 2/5 patients with AIDS related conditions. Biopsies from 5 asymptomatic HIV positive patients and the 6 control subjects were without ultrastructural alterations. The occurrence of TRI was related to low numbers of CD 4+ lymphocytes. 5/7 patients with TRI had elevated serum interferon activity, and in all of the patients without TRI, interferon activity was below detection level. The occurrence of TRI was not dependent on the presence of free p24 antigen in serum. It is concluded that the occurrence of TRI in entothelial cells of skin capillaries is associated with late stages of HIV infection and this may indicate a generalization of this change.

Acquired Immunodeficiency Syndrome

HIV neutralizing antibodies: development and association with HIV related disease.

Serum neutralization was measured in 72 sera collected during a 5.5-year period from 10 HIV infected individuals. Neutralizing antibodies (NA) were present in all sera. NA titers ranging from greater than 40 to greater than 640 were detected in sera from 4 patients, who all remained healthy and further an increase with time of NA was observed in these 4 patients. Progression to disease was observed in 3 persons with NA titers less than or equal to 40 who also lacked or lost anti-gag antibodies. Two of these patients were HIV antigenaemic prior to development of disease, whereas antigen was not detected in the remaining 7 healthy persons. A weak positive correlation (R(S) = +0.643, p less than 0.001) was found between titers of NA and whole virus antibody (WVA), with the ratios between titers (NA titer/WVA titer) varying a 100-fold. The results suggest that the presence of NA in some cases might be related to a healthy carrier state and that a combination of low titer NA with decline of anti-gag antibodies and/or HIV antigenaemia is associated with progression to clinical disease.

Acquired Immunodeficiency Syndrome