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Biomedical subjects

M Fiala

Publications and source records attributed to M Fiala.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Response to treatment with the leukocyte-derived immunomodulator IMREG-1 in immunocompromised patients with AIDS-related complex. A multicenter, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if a 6-month course of therapy with IMREG-1, a leukocyte-derived immunomodulator, slows disease progression in patients with AIDS-related complex. DESIGN: Randomized, double-blind trial. SETTING: Five academic- and three community-based clinics. PATIENTS: Immunocompromised patients (143) with HIV. INTERVENTIONS: IMREG-1 or placebo every 2 weeks (13 doses). MAIN RESULTS: Twelve of forty-eight patients on placebo and 5 of 95 patients on IMREG-1 experienced adverse events (AIDS-defining opportunistic infection or neoplasm, wasting syndrome, HIV-associated encephalopathy, or peripheral sensory neuropathy). Based on an intention-to-treat analysis, Kaplan-Meier event probabilities were 26% for the placebo group and 6% for the IMREG-1 group (P less than 0.001); based on the Cox proportional hazards model, the relative risk for patients on placebo compared with patients on IMREG-1 was 5.1 (95% CI, 1.8 to 14.8). The frequency of symptoms significantly increased from baseline in patients receiving placebo. The mean decrease in CD4+ cells from baseline was 80 x 10(6) cells/L in the placebo group and 29 x 10(6) cells/L in patients on IMREG-1, with 20% (8) and 38% (32) of patients, respectively, showing a trend toward an increase (P = 0.04). In patients receiving IMREG-1, the size and rate of delayed hypersensitivity responses were larger than in the placebo group. CONCLUSIONS: Patients with AIDS-related complex experienced fewer adverse events and constitutional symptoms after IMREG-1 treatment. The slower loss of CD4+ cells and increased size and rate of delayed hypersensitivity responses most likely reflect the effect of IMREG-1 on the immune system. No toxicity related to IMREG-1 administration was observed.

AIDS-Related Complex↗
PubMed1991

Clinical benefits and recovery of delayed-type hypersensitivity in patients with AIDS-related complex treated with IMREG-1 or placebo.

IMREG-1, an immunomodulatory biological therapeutic, was studied in a placebo-controlled, double-blind, six-month trial in 45 anergic patients with AIDS-related complex (ARC) and 4 with Kaposi's sarcoma, which was followed by compassionate IMREG-1 administration to all subjects. The IMREG-1 group had significantly less AIDS-defining events compared with the placebo group during the randomized trial (6.9 events per 100 person-years vs 43.7 events per 100 person-years, P = 0.018, relative risk 6.33) and the total observation period. Patients receiving IMREG-1 significantly improved their work performance. Nine (41%) of 22 patients in the IMREG-1 group, compared with one (14%) of seven in the placebo group, recovered cutaneous reactivity to tetanus toxoid. At the end of the six-month trial, CD4+ counts were 0.429 x 10(9)/l in the IMREG-1 group and 0.304 x 10(9)/l in the placebo group (P = 0.04). IMREG-1 is a promising therapeutic for HIV-infected patients with symptoms of ARC.

AIDS-Related Complex↗
PubMed1991

Multi-step pathogenesis of AIDS--role of cytomegalovirus.

Human immunodeficiency virus (HIV) has been shown to be the initial aetiological agent of the acquired immune deficiency syndrome (AIDS). The recent clinical, epidemiologic, pathological, immunological and molecular data presented in this review point to a multi-step pathogenesis of AIDS involving HIV as an initial cause leading to reactivation of cytomegalovirus (CMV), human herpesvirus-6 (HH-6) and other immunosuppressive organisms. Although the onset of CMV reactivation is not precisely known, it may be related to the transition from AIDS-related complex to AIDS. The molecular interactions between CMV and HIV occur in both directions. Although transcriptional activation of HIV by CMV infection (possibly via induction of NF chi B) is better known, the enhancement of CMV replication by HIV is clinically as important. The interactions between HIV or simian immunodeficiency virus (SIV) and CMV appear to be more specific than between HIV or SIV and other herpes viruses, and are also cell-type-dependent. CMV-induced immune suppression (possibly of variable magnitude with different strains) may be an additional co-factor in AIDS. In a rhesus monkey model, the interaction of SIV with rhesus CMV appears contributory to the reproduction of the full-blown simian AIDS. Patients with AIDS and disseminated CMV infection display the maximum activation of HIV p24 antigenaemia and the greatest deficiency of CD8+ T lymphocytes. Defects in CD4+ and CD8+ T cells, including HIV- and CMV-specific cytotoxic T cells, are crucially important in the progression to terminal AIDS and are related not only to HIV but also to CMV and HH-6 infections of lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex↗
PubMed1990

Lymphangioscintigraphy in AIDS-associated Kaposi sarcoma.

Kaposi sarcoma, a common opportunistic neoplasm complicating AIDS, is thought to arise from the vasculature and possibly from lymphatic endothelium. To evaluate the nature and extent of lymphatic involvement in AIDS-associated Kaposi sarcoma, we used an improved technique of whole-body lymphangioscintigraphy. Six human-immunodeficiency-virus-seropositive men (40-51 years old) with AIDS and extensive Kaposi sarcoma had bilateral foot and/or hand intradermal injection of 0.05 ml of 99mTc-labeled human serum albumin (500 microCi, 18.5 MBq). After sequential whole-body scanning with a digital gamma camera, the findings were interpreted by comparing them with findings from similar studies in 30 other patients without AIDS or Kaposi sarcoma (26 with primary or secondary lymphedema and four with normal extremities). Unlike in normal limbs, where lymphangioscintigraphy displayed early lymphatic truncal and regional nodal filling with radionuclide, in patients with Kaposi sarcoma, lymphangioscintigraphy disclosed a variety of abnormal patterns with some features distinct and others resembling lymphatic dysplasia as seen in primary and secondary lymphedema. These included focal accumulation of tracer within lymphatic channels in the distribution of cutaneous Kaposi lesions; delayed tracer transport with absent, faint, or intense regional lymph nodal uptake; and retarded or impeded lymphatic drainage with tracer intensification in the region of Kaposi sarcoma plaques. The impaired lymphatic drainage and nodal dysfunction seen on scintigrams in patients with AIDS-associated Kaposi sarcoma suggest a close connection between the lymphatic system and this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The detection of HIV by in situ hybridization.

A simplified method of in situ hybridization is described for the detection of HIV targets. This standardized method can be applied to sections of formalin-fixed paraffin-embedded tissues, cell blocks, and smears of cultured cells using 3H- or 35S-labeled DNA and 35S-labeled RNA probes. In order to use elevated stringencies in the hybridization and wash steps, tissue sections and cells are covalently bonded to silanated glass slides without their subsequent loss from the slides. Routine hematoxylin and eosin or Romanovsky's stains enable the identification of the cells detected by in situ hybridization. HIV-infected neuroblastoma and lymphoid cell lines, lymph nodes, bone marrow, kidney, as well as brain tissue from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex are used to demonstrate the generality of the procedure. The standardized method described widens the ease and applicability of in situ hybridization in the investigation of pathologic tissues with the use of diverse specimens and probes.

DNA Probes↗
PubMed1990

AIDS, Kaposi sarcoma, and the lymphatic system: update and reflections.

Based on ongoing basic and clinical investigations, further evidence is presented that the AIDS-Kaposi sarcoma (AIDS-KS) complex involves a progressive disturbance of the blood-lymph circulatory loop of fluid, macromolecules, and migrating cells. We first surveyed the spectrum of vascular abnormalities including Kaposi sarcoma (KS) found in the AIDS/ARC population, then non-invasively imaged lymphatic system abnormalities in AIDS-KS by whole body lymphangioscintigraphy, and finally examined the biologic behavior of AIDS-KS cells in long-term tissue culture. These observations are viewed in terms of the lymphatic and blood vascular route of entry and transport of free and cell-associated virus and other opportunistic pathogens as well as poorly understood host endothelial-immune system interactions.

AIDS-Related Complex↗
PubMed1978

Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients.

Thirty-five renal allograft recipients were studied concerning the relationship between cytomegalovirus (CMV), herpes simplex virus (HSV), and opportunistic bacterial and fungal infections. The incidence of opportunistic infections was determined for patients whose tests prior to transplantation were seronegative in complement fixation and indirect hemagglutination assays of CMV antibody and for those patients whose tests were seropositive. Among the six seronegative patients with seronegative tests, four (66%) experienced active CMV infection within two months, and four died of Candida or Aspergillus infection within six months after transplantation. Among the 22 patients with seropositive tests, only one (4%) had a fungal infection and it was nonfatal (P less than .05). The increased morbidity and mortality due to fungal and bacterial infections in transplant recipients with seronegative CMV tests appears, therefore, to be related to primary CMV infection rather than to generalized immunodeficiency.

Antibodies, Viral↗
PubMed1978

Cytomegalovirus infections in renal allograft recipients: correlative studies with histocompatibility antigens.

We studied 32 renal allograft recipients in order to determine whether or not any correlation could be demonstrated between the HLA and development of cytomegalovirus infection. There was a positive stastical correlation (P less than 0.01) of the development of cytomegaloviraemia and the number of HLA antigens mismatched in the recipient. There was no correlation between specific HLA antigens and predisposition to develop cytomegalovirus infection. The implication of our observations with regard to the pathogenesis of cytomegalovirus infection in renal allograft recipients is discussed.

Adult↗
PubMed1978

Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen.

Complement-fixing (CF) antigen, prepared from cytomegalovirus (CMV)-infected cells and solubilized by urea and Tween-20, was fractionated on agarose gel columns. Its molecular weight was 1.5--5 X 10(7) daltons, and it contained 5 major peptides with molecular weights from 60,000--90,000 daltons. The peptide with a molecular weight of 70,000 daltons which was present in the solubilized CF antigen was absent in a soluble fraction from infected cells without CF activity and may be, therefore, important in this respect. The antigens present in the CF antigen did not elicit neutralizing antibody.

Antigens, Viral↗
PubMed1978

IgE response in heterophil-positive infectious mononucleosis.

Nineteen patients with heterophil-positive infectious mononucleosis were followed with serial blood sampling for an average of 14.6 mo. A preillness serum sample, obtained more than 2 mo before onset of illness, was available from 9 patients. A total of 141 samples were tested under identical conditions for total IgE levels by a paper-disc radioimmunoassay. Hematologic and serologic studies were also done. IgE changes showed a definite pattern, consisting of an elevation early in illness, rapidly followed by a significant drop reaching a nadir by the third month, then gradually returning to the preillness level (PIL) over a period of about a year. On the average, the peak was about 3 times the PIL, and the nadir about half the PIL. The IgE peak always coincided with the peak of atypical lymphocytes, and in no instance did it occur later than the peaks of other hematologic or serologic changes. No definite relationship was noted between IgE levels and the severity of illness. Heterophil-positive infectious mononucleosis is the first well-defined infectious disease found to be associated with such a pattern of IgE response.

Adolescent↗
PubMed1978

Fever of undetermined origin: role of cytomegalovirus and Epstein-Barr virus.

Roles of various infections, neoplasms and granulomatous diseases in fever of unknown origin were studied in 22 patients. Bacterial infections were responsible in seven (32 percent), herpes viruses in five (23 percent), neoplasms in four (18 percent) and granulomata in two (9 percent) cases. Patients with herpes infections had initially no clinical or routine laboratory clues to viral involvement, and were given an intensive workup for 5 to 15 days. The diagnosis was made on the basis of cytomegalovirus or Epstein-Barr virus lgM antibody titers.

Adolescent↗
PubMed1977

Cytomegalovirus mononucleosis in a healthy adult: association with hepatitis, secondary Epstein-Barr Virus antibody response and immunosuppression.

A 35 year old previously healthy physician had clinical manifestations of a mononucleosis illness complicated by arthralgia, vesicular pharyngitis and hepatitis. Initially, the patient had cytomegalovirus (CMV) viremia (predominantly in polymorphonuclear leukocytes) followed by the presence of CMV in the urine, throat and semen. He also had an antibody response to the Epstein-Barr virus which appeared to be a secondary type. During the acute phase of illness, only 7 per cent of the patient's lymphocytes formed spontaneous T cell rosettes as compared to a normal value of 65 to 70 per cent. Concurrently, evidence of abnormal delayed hypersensitivity was manifested by the loss of reactivity to mumps skin test antigen. All clinical and laboratory abnormalities except for the persistence of CMV in the pharynx, urine and semen returned to normal after resolution of the clinical illness.

Adult↗
PubMed1977

Cytomegalovirus retinitis secondary to chronic viremia in phagocytic leukocytes.

We studied the relationship between the duration and intensity of cytomegalovirus viremia, cytomegalovirus complement fixing antibody, and cytomegalovirus retinitis in 61 renal transplant recipients. Five (8%) patients had chronic viremia which lasted more than six months. Two of the five developed typical cytomegalovirus retinitis and a severe fungal infection after intensive viremia of more than 11 months' duration. Retinitis did not develop in 22 patients with short-term viremia. Infectious cytomegalovirus was largely associated with polymorphonuclear leukocytes, but the virus was associated with monocytes during the immature granulocytic response accompanying one patient's terminal illness.

Adult↗
PubMed1977

Effect of cytosine arabinoside on Herpes virus infection in renal allograft recipients.

Cytosine arabinoside (Ara-C) was used for treatment of severe symptomatic cytomegalovirus (CMV)-herpes infections that were seen in nineteen of 174 renal allograft recipients. Ara-C was administered by continuous intravenous infusion at a mean dose of 35 mg/m2 daily for three to four days. Side effects were few and minor in nature. All cases of herpes simplex and herpes zoster, which usually have a prolonged and sometimes unfavorable course in immunosuppressed patients, cleared promptly with no recurrence. All nine patients, except one who had CMV infection with the symptom complex of fever and retinitis or pneumonitis, responded satisfactorily. In the three patients in whom the CMV titers were available, there was a significant decrease in titer within two weeks after treatment. This pilot study of Ara-C in treatment of CMV-herpes infections in immunosuppressed renal allograft recipients suggests a degree of efficacy and safety in the drug that would justify a carefully designed, controlled study.

Adult↗
PubMed1977

Extrinsic modulation of human T-lymphocyte E rosette function associated with prolonged hepatocellular injury after viral hepatitis.

Defective T-lymphocyte E rosette (ER) function associated with viral hepatitis A and B may be due to mechanisms extrinsic or intrinsic to the target lymphocyte. The extrinsic defect is induced by an immunoregulatory plasma lipoprotein (RIF) and has the capacity to regenerate ER function in vitro. The intrinsic defect is refractory to regeneration and is not associated with RIF. Although both mechanisms occur with high frequency during the acute phase of viral hepatitis they tend to segregate in accordance with progression of hepatocellular injury at later stages of the disease. The extrinsic defect was observed in 7 out of 8 patients with longstanding chronic active hepatitis and in 10 out of 10 patients with unresolved hepatitis 12 wk after the onset of jaundice. In contrast, none of nine patients with resolved hepatitis had extrinsically defective ER function 12 wk after the onset of jaundice whereas eight of them displayed an intrinsic defect of ER function at that time. Among the various viral and liver diseases studied RIF appeared to be specific for hepatitis A and B viral infections. None of 64 sera from a variety of viral infections including Epstein-Barr virus cytomegalovirus mononucleosis with associated hepatitis nor 15 sera from patients with several chronic nonviral liver diseases were positive for RIF. RIF and its associated extrinsic defect in ER function therefore appear to correlate with a particular type of hepatocellular injury initiated by the hepatitis A and B viruses that may have a propensity for persistence and(or) progression to an aggressive form of chronic hepatitis.

Acute Disease↗