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Biomedical subjects

P Aukrust

Publications and source records attributed to P Aukrust.

125 records · Page 7Linked to original sources

Duodenal intraepithelial gamma/delta T cells and soluble CD8, neopterin, and beta 2-microglobulin in serum of IgA-deficient subjects with or without IgG subclass deficiency.

Expression of the gamma/delta T cell receptor (TCR) on CD3+ intraepithelial lymphocytes (IELs) was studied by two-colour immunofluorescence in duodenal tissue sections from healthy (n = 6) or infection-prone (n = 7) subjects with selective IgA deficiency (IgAD), and subjects (n = 4) with combined IgAD and IgG subclass deficiency. TCR gamma/delta+ IEL proportions in selective IgAD subjects (median 6.3%, range 1.0-41%) and in those with combined deficiency (median 4.5%, range 1.2-33%) were well within the range (0.3-38%) for histologically normal controls (n = 11), but the healthy IgAD subgroup tended to show raised TCR gamma/delta+ IEL proportions (median 13.6%) compared with the other two subgroups. Also the number of TCR gamma/delta+ IELs per intestinal length unit was relatively high (median 13.9/mm) in the healthy IgAD subjects, and significantly raised (P < 0.03) compared with controls (median 3.2/mm). Paired staining revealed that most TCR gamma/delta+ IELs in both selective IgAD (98%) and combined deficiency (99%) were CD8-, and a large fraction (median 84% and 63%, respectively) expressed the V delta 1/J delta 1-encoded epitope. The total number of CD3+ IELs (mostly CD8+) was similar to controls. IgAD subjects, and especially the healthy subgroup, had significantly increased serum concentrations of soluble CD8 (P < 0.0002), neopterin (P < 0.005), and beta 2-microglobulin (P < 0.007), which was similar to our previous observations in common variable immunodeficiency, and probably reflected stimulation of cell-mediated immunity. In addition, the increased TCR gamma/delta+ IELs might reflect a component of compensatory surface protection in the healthy IgAD subgroup.

Adolescent↗

[Natural products can be hazardous to health].

Side effects of herbal and health food products have been infrequently reported such as hepatic damage after use of such products. Four such patients were treated in our department in the course of two years. In all four patients, the use of herbal remedies was the probable cause of serious hepatic damage, but both etiology and pathogenesis were difficult to establish. Two major areas of concern are inaccurate formulation and contaminated preparations. As long as no therapeutic effect can be demonstrated from this type of medicine, serious side effects are unacceptable. A critical attitude should be adopted towards these medicines and the use of them.

Adult↗

Left atrial myxoma and systemic AL-amyloidosis.

A case of left atrial myxoma with systemic AL-amyloidosis is described. Localized myxomas have the peculiar property of giving rise to constitutional symptoms, indicating a systemic disease process. The coexistence of AL-amyloidosis and an atrial myxoma in the same patient makes it tempting to suggest that an immunological defect is involved in the development of both diseases.

Aged↗

Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features.

Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P less than 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs = -0.61, P less than 0.005 and rs = -0.83, P less than 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs = -0.58, P less than 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.

Adolescent↗

Cytomegalovirus (CMV) pneumonitis in AIDS patients: the result of intensive CMV replication?

We report a case of fatal pulmonary disease in a patient infected with human immunodeficiency virus (HIV), where cytomegalovirus (CMV) was the only causative agent identified in the lungs at autopsy. The most prominent histopathological features were numerous interalveolar cells containing CMV inclusion bodies combined with scanty signs of inflammation. We propose that the lung damage caused by CMV in acquired immune deficiency syndrome (AIDS) patients is a direct consequence of cytopathogenic effects of the virus related to the extent of active virus replication.

Acquired Immunodeficiency Syndrome↗

[Symptomatic cytomegalovirus infection in patients with acquired immunodeficiency syndrome].

During a seven-year period, symptomatic cytomegalovirus (CMV)-infection was diagnosed in 21.5% (n = 10) of all AIDS patients at the National Hospital of Norway (retinitis n = 8, colitis n = 3, pneumonitis n = 2, gastritis n = 1). Symptomatic cytomegalovirus-infection was associated with a poor long-term prognosis (median survival 174 days, range 10-415). Median CD4+ lymphocyte counts at onset of symptomatic cytomegalovirus-infection was 24 x 10(6)/l (range 6-68). Regular ophthalmological examination of HIV-infected patients with severe immunodeficiency, and endoscopy with multiple mucosal biopsies in patients with suspected cytomegalovirus-infection of the gastrointestinal tract, were of major importance in diagnosing symptomatic cytomegalovirus-infection. Six patients received an induction course of ganciclovir, and foscarnet was administered in two patients due to leukopenia. Problems of toxicity to the available anti-CMV agents make the development of additional therapeutic approaches desirable.

Acquired Immunodeficiency Syndrome↗

[Cytomegalovirus disease in the gastrointestinal tract].

Cytomegalovirus infections in immunocompromised patients may cause serious illness, particularly in patients with HIV-disease and in transplant recipients. There is an increasing number of reports of cytomegalovirus infections involving the alimentary tract, especially colitis. Diagnosis of cytomegalovirus disease is at present based on specific histological findings. Antibody findings can be difficult to interpret. The slow growth of cytomegalovirus in cultures makes this method less useful in the acute setting of diagnosis. It is important to recognize cytomegalovirus colitis as a differential diagnosis to idiopathic inflammatory bowel disease. In fulminant disease, colectomy should be considered in addition to antiviral treatment.

Colon↗

[Cytomegalovirus disease in the upper gastrointestinal tract. Endoscopic findings].

Cytomegalovirus disease is seen mainly in immunocompromised patients. While gastrointestinal symptoms are difficult to interpret, the typical finding at endoscopy of the upper alimentary tract is ulcers. Diagnosis of cytomegalovirus disease is based on typical histological findings in biopsy specimens. Antiviral treatment should be started when cytomegalovirus disease is detected in transplant patients. If it is decided to treat patients suffering from AIDS, lifelong maintenance treatment is required. Early diagnosis by means of endoscopy and biopsies is very important, and will decide the outcome of instituted treatment.

Acquired Immunodeficiency Syndrome↗

Fatal cytomegalovirus (CMV) colitis in a patient receiving low dose prednisolone therapy.

Cytomegalovirus (CMV) colitis is uncommon in patients who are not gravely immunodepressed. We report a case of fatal CMV colitis in a 54-year-old woman on low dose steroid therapy. She was admitted to hospital after sudden onset of abdominal pain and hemorrhagic watery diarrhea. After 25 days in the hospital, treatment with high dosage of methylprednisolone was started for presumed ulcerative colitis. Her condition worsened and she died 52 days after admission. It is important to recognize CMV colitis as differential diagnosis to inflammatory bowel disease, particularly when the colitis is refractory to immunosuppressive treatment.

Arthritis↗

[Acyclovir-resistant herpes simplex virus].

Infection with acyclovir-resistant herpes simplex-virus is now a clinical reality in patients with AIDS or who are otherwise immunocompromised. The most common mechanism of resistance is selection of mutants with inability to express thymidine kinase activity. Vidarabine, foscarnet and gancyclovir can be used to treat infections with acyclovir resistant virus. In recent years there have been many reports of drug resistance from the treatment of other virus infections too.

Acyclovir↗

[HIV and the central nervous system].

It is well documented that human immunodeficiency virus (HIV) can infect the central nervous system. Neurological dysfunction occurs frequently in acquired immunodeficiency syndrome (AIDS) and most commonly in the form of a subacute HIV-encephalitis. The pathological abnormalities in patients with subacute HIV-encephalitis are most prominent in subcortical structures, notably in the cerebral white and deep gray matter. The patients frequently develop abnormalities in cognitive, motor and behavioral functions. The infected cells are predominant lymphocytes and macrophages. The production of cytokines by these cells appears to be a central factor in the pathogenesis of subacute HIV-encephalitis. The central nervous system can function as a reservoir of HIV infection. Neuropsychological assessment is a sensitive method for documentation of early brain involvement by HIV infection. The HIV-associated neurological abnormalities may be partially ameliorated by administration of zidovudine (AZT).

Encephalitis↗

[Intestinal spirochaetosis].

It is well known that spirochetes may be found in the digestive tract of various species, including humans. We describe a homosexual man with long-standing diarrhoea, probably caused by intestinal spirochaetosis. The diagnosis was based upon light microscopic demonstration of a thin haematoxyphilic bandlike layer covering the intestinal surface epithelium, which is an established diagnostic characteristic of intestinal spirochaetosis. The spirochaetosis was further confirmed by electron microscopy. The pathogenetic significance of spirochetes in human intestinal disease is not fully understood. However, intestinal spirochaetosis should be suspected in patients with long-standing diarrhoea. Symptomatic spirochaetosis in the gut responds well to treatment with metronidazole. The spirochetes of the human digestive tract constitute a newly defined genus of the family Treponemataceae.

Adult↗

[Viral or bacterial meningitis. Differential diagnostic problems].

A 19 year old previously healthy man presented symptoms of meningitis. Culture from the cerebrospinal fluid revealed herpes simplex virus type 2 to be the responsible agent. The course was benign, the patient was never seriously ill. He recovered fully within a few weeks. The cerebrospinal fluid showed prolonged pleocytosis and low values of glucose. The traditional cerebrospinal fluid parameters employed in the diagnosis of meningitis, and for distinguishing bacterial from viral meningitis, are shown to be inadequate in many cases. Of these tests cerebrospinal fluid differential cell count is of most value, especially if repeated after 12 hours or so in the initial course. Additional tests have been proposed, none of which have proven to be of much help, except perhaps the test for lactate in the cerebrospinal fluid.

Adult↗

[Herpes simplex virus infection of the central nervous system].

Herpes simplex virus type 1 (HSV 1) infection in the central nervous system results in encephalitis with high mortality and morbidity. However herpes simplex virus type 2 (HSV 2) infection in this area usually results in benign meningitis. Brain biopsy is the most sensitive and most specific method for diagnosing HSV 1 encephalitis. Antibody determinations in serum and cerebrospinal fluid give only a retrospective diagnosis. A rapid non-invasive diagnostic test is urgently required as an alternative to biopsy. Cerebrospinal fluid viral culture may be of great help in diagnosing HSV 2 meningitis. Acyclovir given intravenously is the treatment of choice for HSV encephalitis. In the case of HSV 2 meningitis no studies have been conducted on systemic antiviral therapy.

Biopsy↗

Activation of tumor necrosis factor--alpha system in HIV-1 infection: association with markers of immune activation.

The relationships between serum levels of soluble tumor necrosis factor receptors (sTNFRs) and other prognostic and immunological parameters in different immunological subgroups of 64 HIV-1 infected patients were studied. In the patient group as a whole, the raised serum levels of sTNFRs were significantly inversely correlated to the numbers of CD4+ and CD8+ lymphocytes and significantly positively correlated with serum levels of neopterin, HIV-1 p24 antigen and the soluble CD8/CD8+ lymphocyte ratio. However, when the patients were classified into three separate immunological subgroups according to the numbers of CD4+ lymphocytes, only serum levels of neopterin were significantly correlated to levels of sTNFRs in all the defined immunological subgroups. These results indicate that HIV-1 infection is associated with a persistent and chronic immune activation in the TNF system manifested by raised serum levels of sTNFRs, which may reflect sustained activation of the immune system particularly in monocytes/macrophages. Further, these results confirm that, when comparing immunological and virological parameters in HIV-1 infection, different results may be obtained in different immunological subgroups of patients.

Adolescent↗

The effect of 1,25-vitamin D3 on maturation of monocytes from HIV-infected patients varies with degree of immunodeficiency.

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), has been shown to induce monocyte-to-macrophage maturation in vitro as well as monocytic differentiation of bone marrow precursors and monocytic leukaemic cell lines. In this study we assessed whether 1,25D could improve the maturation defect we have previously demonstrated in monocytes from AIDS patients. In vitro growth and maturation of monocytes from 10 controls, 15 asymptomatic HIV positives (CDC group II or III) and 13 symptomatic HIV positives (CDC group IV) was examined by assessing cellular morphology, differentiation, adherence and protein content. Cells were cultured for 10 days with or without addition of 1,25D at a concentration of 100 pg/ml. In addition, patients were monitored clinically and by immunological parameters and HIV p24 antigen in serum. The present study showed that addition of 1,25D significantly improved the growth and maturation in both patient and control groups. There was a significant negative correlation between response to 1,25D and CD4+ lymphocyte count in blood in HIV-infected patients. A greater response to 1,25D was seen in monocytes from patients with advanced immunodeficiency and symptomatic disease than in monocytes from asymptomatic patients. However, in the most advanced cases of HIV infection with serious ongoing opportunistic infections the response to 1,25D was very poor, possibly reflecting profound and incorrigible dysfunction of monocytes.

Adult↗