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Biomedical subjects

F D Goebel

Publications and source records attributed to F D Goebel.

At least 91 records · Page 5Linked to original sources
PubMed1996

High predictive value of Toxoplasma gondii IgG antibody levels in HIV-infected patients for diagnosis of cerebral toxoplasmosis.

The results of serological tests for Toxoplasma gondii IgG in 31 HIV-infected patients with toxoplasmic encephalitis (TE) and 49 HIV-infected patients seropositive for Toxoplasma gondii but without TE were compared. All patient had a CD4+ lymphocyte count < 150/microliters. Of the TE patients, 22 (71%) were designated as having relatively high IgG levels on the basis of the following Toxoplasma IgG titre combination: Sabin-Feldman test > or = 1:256, indirect hemagglutination test > or =1:1024, direct agglutination test > or = 1:14,580. Only 3 patients without TE had relatively high IgG titres. Relatively high IgG titres indicated TE with a positive predictive value of 88% in HIV-infected patients with CD4+ cell counts < 150/microliters, and could be observed in most patients several months prior to the first clinical and radiological signs of TE.

AIDS-Related Opportunistic Infections↗
PubMed1996

A new quantitative RT-PCR assay for the vasoconstrictor endothelin.

Endothelin has been found to be the most powerful and important factor regulating vasoconstriction in normal and pathological conditions. Rapid degradation and very low concentrations make it difficult to use even very sensitive enzymatic or immunochemical assays for this oligopeptide. We have established a quantitative polymerase chain reaction (PCR) assay for the mRNA of endothelin-1 (ET-1), the best characterized of the three endothelin isoforms known so far. Using human umbilical vein endothelial cells as source for endothelin, the absolute number of ET-1 cDNA molecules serving as template for the amplification reaction can be calculated with the aid of an internal standard as competitor for the PCR primers, while relative amounts of ET-1 mRNA are estimated with a new solid-phase enzyme-linked immunosorbent assay for the PCR product of ET-1 and a constitutively expressed single copy gene product, beta-actin. The combination of these supplementary assay systems allows the analysis of endothelin-1 mRNA regulation on a very sensitive level.

Actins↗
PubMed1996

Tuberculosis among European patients with the acquired immune deficiency syndrome. The AIDS in Europe Study Group.

OBJECTIVES: To describe the characteristics of acquired immune deficiency syndrome (AIDS) patients with tuberculosis in Europe; to assess the incidence and risk factors of tuberculosis after AIDS; to compare survival of AIDS patients with and without extra-pulmonary tuberculosis (EPTB) at the time of AIDS diagnosis. DESIGN: Multicentric retrospective cohort study of 6544 AIDS patients diagnosed in 52 clinical centres and 17 European countries. METHODS: Description of patient characteristics and comparisons of tuberculosis incidence and mortality after AIDS with multivariate Cox proportional hazard models. RESULTS: 14.6% of AIDS patients had tuberculosis and 78% of those with tuberculosis had EPTB. EPTB was the AIDS-defining condition in 8.7% of the patients. Tuberculosis incidence after AIDS was 3.1 per 100 person-years. Age, gender and HIV-transmission category were not significantly associated with an increased risk of tuberculosis and the strongest risk factor for both EPTB and pulmonary tuberculosis (PTB) was the region of origin. The adjusted hazard ratio of EPTB and PTB in Southern Europe compared to Northern Europe were 5.5 (95% confidence interval [CI]: 5.0-6.1) and 2.0 (CI: 1.4-2.7) respectively. The apparent survival advantage of AIDS patients with EPTB compared to patients diagnosed with other conditions (median survival time: 22 vs 16 months) was statistically not significant when confounding variables were adjusted for (Hazard ratio: 0.85; CI: 0.62-1.07). CONCLUSIONS: In Europe, there are large differences in the incidence of tuberculosis among AIDS patients in different countries. They do not seem to be due to differences in age or in the prevalence of injecting drug use and likely reflect differences in the prevalence of tuberculosis infection. The role of recent transmission should also be considered, and national tuberculosis control efforts and Europe-wide surveillance need to be reinforced accordingly.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Efficacy and safety of Stealth liposomal doxorubicin in AIDS-related Kaposi's sarcoma. The International SL-DOX Study Group.

The utility of current chemotherapeutic regimens in the treatment of AIDS-related Kaposi's sarcoma (AIDS-KS) is often compromised by both limited efficacy and substantial toxicity. Pegylated (Stealth) liposomal doxorubicin hydrochloride (SL-DOX) has been demonstrated specifically to deliver high concentrations of doxorubicin to Kaposi's sarcoma (KS) lesions. This phase II study was performed to evaluate the efficacy and safety of SL-DOX in the treatment of moderate to severe AIDS-KS. Patients were treated biweekly with 10, 20, or 40 mg m-2 SL-DOX. Tumour response was assessed according to AIDS Clinical Trials Groups (ACTG) criteria before each cycle. Best response was determined for 238 patients and was achieved after a mean of 2.3 cycles (range 1-20). Fifteen patients (6.3%) had a complete response to SL-DOX, 177 (74.4%) had a partial response, 44 (18.5%) had stable disease and two (0.8%) had disease progression. SL-DOX was well tolerated: ten patients discontinued therapy because of adverse events, in four cases because of neutropenia. Grade 3 or 4 neutropenia occurred after 281 of 2023 cycles (13.9%) but involved 137 of 240 patients (57.1%) for whom data were available. SL-DOX has substantial activity in AIDS-KS. Best response is typically seen after fewer than three cycles of chemotherapy and in some cases may be prolonged. The most important adverse event is neutropenia, which occurs after a minority of cycles but which may occur in over half of all patients.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Deficits in perimetric performance in patients with symptomatic human immunodeficiency virus infection or acquired immunodeficiency syndrome.

PURPOSE: We measured the perimetric performance in patients with either acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease but without AIDS. METHODS: Light-difference sensitivity in the central field was measured in 74 eyes of 37 patients. The Humphrey Field Analyzer 640, program 30-2 was used. Additionally, 143 eyes of 143 normal control subjects were studied. RESULTS: Mean deviation was significantly reduced in patients with HIV disease compared with control subjects (mean +/- S.E.M., -4.30 +/- 0.52 vs -0.77 +/- 0.15, respectively; P < .0001). Analysis of subgroups demonstrated that patients with lymphadenopathy syndrome or AIDS-related complex (N = 40 eyes; -3.52 +/- 0.41; P < .0001) as well as patients with AIDS (N = 34 eyes; -5.23 +/- 0.97; P < .0001) had a reduced mean deviation. Those comparisons remained significant (P < .0001) when data were analyzed independently for the right eyes and for the left eyes. Corrected pattern standard deviation (3.15 +/- 0.30 vs 1.39 +/- 0.09; P < .0001) was higher in patients with HIV disease compared with control subjects. Again, analysis of subgroups disclosed a significant increase in patients with lymphadenopathy syndrome or AIDS-related complex (2.55 +/- 0.36; P < .0001) as well as in patients with AIDS (3.85 +/- 0.51; P < .0001). Both comparisons remained significant when data were analyzed independently for the right and left eyes. CONCLUSIONS: This study demonstrates visual dysfunction despite normal visual acuity in patients with HIV disease. Our results are consistent with the hypothesis of damage at the neuroretinal level.

AIDS-Related Complex↗
PubMed1995

Sicca syndrome in patients infected with the human immunodeficiency virus.

PURPOSE: To investigate an association of the severity of the human immunodeficiency virus (HIV) disease with decreased tear production in a controlled setting. PATIENTS AND METHODS: Seventy-two patients (144 eyes) and 30 age- and sex-matched control subjects (60 eyes) were studied prospectively. Tear production was measured using the Schirmer I test (measured in millimeters after 5 minutes). Patients were classified into three clinical groups: asymptomatic HIV infection, lymphadenopathy syndrome (LAS) or acquired immune deficiency syndrome (AIDS)-related complex (ARC), and AIDS. Additionally, patients were classified according to the CD4+ lymphocyte count. RESULTS: Tear production (mean +/- standard deviation) did not differ (P = 0.32) among eyes of patients with asymptomatic HIV infection (17.1 +/- 10.8; n = 14), LAS or ARC (18.3 +/- 10.3; n = 70), and AIDS (20.7 +/- 10.3; n = 60). In addition, mean tear production was not decreased significantly when comparing each clinical group with the control subjects (17.8 +/- 4.4). However, the relative frequency of eyes with significantly decreased tear production (< 9 mm) was 23.6% in all 144 eyes. In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.52) between eyes of patients with asymptomatic HIV infection (35.7%), LAS or ARC (21.4%), and AIDS (24.1%). In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.30) between eyes of patients with a CD4+ count of more than 400 cells/microliters (23.1%; n = 26), 400 to 200 cells/microliters (31.3%; n = 48), 200 to 50 cells/microliters (14.3%; n = 42), and less than 50 cells/microliters (21.4%; n = 28). CONCLUSION: The authors data show that decreased tear production occurs in approximately 20% to 25% of patients with HIV infection. This increased frequency of decreased tear production is not associated with the CD4+ count, or related to the severity of HIV disease, respectively. The possibility of an autoimmune-like pathogenesis of abnormalities of tear production in patients with HIV infection should be studied intensively.

Adult↗
PubMed1995

Endoscopic ultrasound in the diagnosis and staging of gastrointestinal Kaposi's sarcoma.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has been evaluated for diagnosing and staging of a variety of gastrointestinal tumors, but there are no data on EUS in Kaposi's sarcoma (KS). The aim of the present study was to evaluate the role of EUS in addition to endoscopy in the diagnosis and staging of patients with established or suspected upper gastrointestinal KS. PATIENTS AND METHODS: 22 male acquired immune deficiency syndrome (AIDS) patients were prospectively studied, three of them before and after chemotherapy with liposomal doxorubicin. The features of gastrointestinal KS were recorded, and EUS was assessed for diagnosis in endoscopically negative or inconclusive cases, and for staging in endoscopically visible KS lesions. RESULTS: The typical EUS feature of KS was a hypoechoic and nonhomogeneous lesion leading predominantly to mucosal and submucosal thickening, whereas a few lesions presented only with submucosal involvement. EUS detected suspicious lesions in two patients with negative endoscopy, which turned out to be KS on follow-up. Restaging after chemotherapy in three patients showed regression of lesions both on endoscopy and EUS. CONCLUSIONS: EUS may contribute to better detection of early KS lesions and a more reliable delineation of the extent of gastrointestinal KS, which is valuable for assessing the effect of various forms of therapy.

Adult↗
PubMed1995

[Ocular microangiopathy syndrome in patients with AIDS is associated with increased plasma levels of the vasoconstrictor endothelin-1].

OBJECTIVE: Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients suffering from the acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes including cotton-wool spots are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving vascular structures. METHODS: We studied 29 patients with AIDS by indirect ophthalmoscopy and by slit lamp biomicroscopy, and endothelin-1 immunoreactivity (IR) was measured in plasma by radioimmunoassay. Cotton-wool spots were counted as indicator of retinal microvasculopathy. Conjunctival bloodflow sludging in conjunctival vessels was measured by a standardized rating scale as indicator of conjunctival microvasculopathy. Parameters of immunosystemic damage were determined as covariates. RESULTS: Endothelin-1 IR was closely associated with the number of cotton-wool spots (Spearman r = 0.53, p < 0.01) and with the extent of conjunctival blood-flow sludging (r = 0.61, p < 0.001). The level of significance became stronger applying analysis of covariance with Endothelin-1 IR as dependent variable and number of cotton-wool spots (p < 0.0001) or extent of conjunctival blood-flow sludging (p < 0.0001) as independent variables. CONCLUSION: Our data are consistent with the hypothesis that the vasoconstrictor endothelin-1 has an important role in the pathogenesis of HIV-1-related ocular microangiopathic syndrome. As HIV-1-related ocular microangiopathic syndrome is associated with neuroretinal and cognitive deficits in patients with HIV-1 disease the therapeutic use of endothelin antagonists currently under investigation should be discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Factors associated with the development of Pneumocystis carinii pneumonia in 5,025 European patients with AIDS. AIDS in Europe Study Group.

This study examined the factors associated with the development of a first episode of Pneumocystis carinii pneumonia (PCP) in 5,025 patients with AIDS, including 1,976 patients with primary PCP at the time of AIDS diagnosis and 635 with primary PCP occurring subsequently. Compared with untreated patients, patients treated with zidovudine were at similar risk of developing PCP during the first year of therapy but were at greater risk after longer intervals of treatment. The following factors were associated with an increased risk of PCP (either at the time of AIDS diagnosis or thereafter): lack of primary PCP prophylaxis, male homosexuality/bisexuality, diagnosis of AIDS in northern Europe, and CD4 cell count below 200 x 10(6)/L at the time of AIDS diagnosis. Patients with severe weight loss had a 60% higher risk of developing PCP during follow-up than those without such weight loss. Thus, the occurrence of PCP depended on geographic location, mode of acquisition of human immunodeficiency virus and AIDS, degree of immunodeficiency, and use of various treatment regimens.

AIDS-Related Opportunistic Infections↗
PubMed1995

Human immunodeficiency virus-related microvasculopathy and Kaposi's sarcoma: a case-control study.

Ocular microangiopathic syndrome including retinal and conjunctival abnormalities is frequently found in patients with human immunodeficiency virus type 1 (HIV-1) disease. Kaposi's sarcoma (KS) is the most frequent neoplasia found in patients with HIV-1 disease. We have recently reported a significant association between conjunctival microvasculopathy and KS in 117 patients with HIV-1 disease. The objective of the present study was to determine whether this association is existent when matched patients with and without KS are compared. A total of 22 matched pairs were obtained under consideration of the absolute CD4+ lymphocyte count, Walter Reed (WR) classification, gender, and serum levels of beta-2-microglobulin and neopterin. Conjunctival microangiopathy was determined for each eye by a standardized rating scale ranging from 0 to 5, allowing a reliable and valid quantification of conjunctival blood-flow sludging. The mean value obtained for conjunctival sludge was 1.8 (SEM, 0.4) for patients without KS and 3.2 (SEM, 0.3) for patients with KS, demonstrating a clinically and statistically significant difference between the two groups (Student's t = 3.0; P = 0.003). This difference was higher when patients with a CD4+ lymphocyte count exceeding 200/microliters were regarded. Similar factors or mechanisms may contribute to HIV-related conjunctival microvasculopathy and KS.

Adult↗
PubMed1995

[Incidence and etiology of psychotic disorders in HIV infected patients].

There are numerous case reports on psychoses in AIDS patients and, although more seldom, also in HIV-positive patients in early stages of infection; however, systematic investigations on the frequency, e.g., relevant for the indication of an HIV test in psychiatric patients, are missing. For this study, 1046 HIV-positive patients were examined regarding psychoses. A total of 301 patients (28.8%) were HIV-positive but asymptomatic, and 380 patients (36.2%) had the lymphadenopathy syndrome. One hundred thirty-two patients (12.6%) suffered from an AIDS-related complex and 233 patients (22.3%) from AIDS. Of these 1046 patients, only 9 (0.9%) suffered from psychoses. One patient with a paranoid-hallucinatory syndrome was asymptomatic; one in the lymphadenopathy syndrome was manic. The other 7 patients were all in late stages of the infection. A causal relationship between HIV infection and psychosis and probable in only 3 patients. These data do not indicate a markedly elevated prevalence of psychosis in HIV-positive or AIDS patients.

AIDS Dementia Complex↗
PubMed1995

Combination therapy from a clinician's perspective.

A number of important scientific questions have been answered in recent years concerning how HIV causes disease and whether combinations of antiretroviral agents might be more effective than monotherapies. However, a considerable number of questions remain unanswered regarding when to start treatment and what regimen to start with. It is also obvious that significant disparity exists between what is possible in therapeutic terms, in the clinic, and what has been demonstrated in in vitro studies and clinical trials. In translating what we have learned about combination therapy in clinical trials to application in a clinical setting, it is necessary to consider a number of important factors. First, the availability of antiretroviral agents as licensed products varies considerably between countries, as do the indications for these agents. Physicians in many countries are presently faced with prescribing therapeutic regimens that are already known to be suboptimal. With the speed of release of new data, there is growing disparity between our therapeutic knowledge and what is possible in the clinic. Patient compliance is also a very important consideration in the development of combination therapy, as patients may be expected to take large numbers of tablets for very long periods of time. Trials of combination therapies to date have already provided some insight into patients' willingness to comply with dosing regimens. A further consideration for physicians treating early-stage patients for prolonged periods is the prevention of development of HIV-associated CNS disease. Zidovudine is effective in preventing the onset of AIDS-dementia complex but little is known about the efficacy of other antiretroviral agents. To prevent the re-emergence of this disease to levels seen before the introduction of zidovudine (AZT) in 1987, it might be important to include AZT in all combination therapy regimens. For combination therapy to be approved and used on a widespread basis, effective tools or markers for monitoring the efficacy of therapeutic regimens are required. Tools such as viral load measurements require regulatory approval on a worldwide scale and should be economically and logistically accessible for regular use in the clinic. The increase in cost of HIV management associated with combination therapy is a significant factor in determining its widespread acceptance. It is heartening to see that collaborative efforts are already under way to address this important issue.

AIDS Dementia Complex↗
PubMed1995

[Endoscopy of the upper gastrointestinal tract in HIV disease].

Gastrointestinal (GI) symptoms are part of the most frequent complaints in HIV disease. A methodical effort is required to identify treatable syndromes. Progressive immunodeficiency is associated with increased prevalence of opportunistic or non-opportunistic infections and neoplasms. Dysphagia and odynophagia, in the majority due to candida esophagitis, are best evaluated by endoscopy. In the presence of diarrhea, upper GI endoscopy is indicated if evaluations of stool and endoscopy of the lower GI tract are negative and may uncover proximal small-bowel infection by Cryptosporidium, Microsporidium or Mycobacterium avium. HIV-associated neoplasias (Kaposi's sarcoma, non-Hodgkin lymphomas), not rarely affecting the upper GI tract and sometimes leading to obstruction or bleeding, are reliably diagnosed only by endoscopy. Since visible lesions mostly are nonspecific and normal-appearing mucosa may harbor pathogens, biopsies for pathology and cultures are crucial for correct diagnosis in GI diseases of HIV-infected patients.

AIDS-Related Opportunistic Infections↗