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Biomedical subjects

F D Goebel

Publications and source records attributed to F D Goebel.

At least 145 records · Page 8Linked to original sources

2.5 years survival with sequential ganciclovir/foscarnet treatment in a patient with acquired immune deficiency syndrome and cytomegalovirus retinitis.

The case with the longest survival time (30 months) after the diagnosis of cytomegalovirus retinitis in a group of 53 patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis (median survival time 8.4 months) is described. The patient developed cytomegalovirus retinitis in his left eye and received intravenous virustatic treatment for 29.5 months. Treatment was started with ganciclovir. After withdrawal from maintenance treatment, a relapse of cytomegalovirus retinitis occurred, which was again successfully treated with ganciclovir. A secondary cataract developed, and cataract extraction was performed. After 12.5 months on treatment with ganciclovir, a change to foscarnet was necessary because of neutropenia. Maintenance treatment with foscarnet was well tolerated for 17 months. The cytomegalovirus retinitis showed no signs of reactivation during this period. Vision in the right eye was preserved until death, and no sign of cytomegalovirus retinitis developed in the right eye. This case report demonstrates that an unusual long survival time is possible in a patient sequentially treated with ganciclovir and foscarnet.

AIDS-Related Opportunistic Infections↗

[HIV-associated lymphomas].

Forty-one HIV-positive homosexual men (mean age 39.8 [23-72] years) with malignant lymphomas were examined with the object of exploring the clinical and pathological spectrum of HIV-associated lymphomas in Central Europe, and their therapeutic aspects. There were 33 patients with non-Hodgkin lymphoma of high malignancy and four with non-Hodgkin lymphoma of low malignancy; four further patients suffered from Hodgkin's disease. 27 patients died during the period of observation. The mean survival period after diagnosis was 5.5 months. It depended on the stage reached by the lymphoma at the time of diagnosis: 11.8 months in stage I, 10.6 months in stage II, 7 months in stage III, 3.3 months in stage IV and 1.3 months in patients with primary involvement of the central nervous system by the lymphoma. Eight out of nine patients with highly malignant non-Hodgkin lymphoma in stage I or II attained complete and lasting remissions after chemotherapy or irradiation. However, only minimal prolongation of life was achieved in the 16 patients with lymphomas in stages III or IV. The response rate among all patients treated (complete and partial remissions) was 75%; 45% achieved complete remission. Hodgkin's disease responded well to standard therapy, but the disease rapidly recurred in every case.

Adult↗

Remarkable improvement of neuropsychiatric symptoms in HIV-infected patients after AZT therapy.

Treatment of neuropsychiatric symptoms with AZT (Azidothymidine) seems to be effective in many AIDS patients. In earlier studies, 204 of 525 patients treated with AZT showed neuropsychiatric improvement. In this presentation, two patients with affective disorder and dementia are described. Both patients showed remarkable improvement of their severe psychiatric symptoms after AZT. The authors recommend treatment of AIDS-associated dementia and psychoorganic symptoms with AZT.

AIDS Dementia Complex↗

Serological markers as prognostic criteria for the course of HIV infection.

576 serum samples from 139 HIV infected patients were analyzed for the presence of HIV antigens, as well as anti-core, anti-env and neutralizing antibodies. The results were correlated with the clinical and immunological stages of the patients. While almost all sera were positive for anti-env antibodies, only two thirds of the same sera had antibodies to core proteins. The average antibody titres, particularly of anti-core antibodies, decreased with the onset of clinical symptoms. The presence of p24 antigen could be demonstrated in only 16% of the sera. A positive reaction for core antigen seemed to be correlated with the absence of anti-core antibodies. Env specific neutralizing antibodies were found to be present in all of the sera analyzed in the LC5-test with a maximum neutralizing capacity observed in sera from WR 4 patients. A useful serological marker must fulfil two criteria, namely positive reactivity in the majority of sera examined and a broad range of antibody titres. None of the above described parameters meet these demands. Here we describe the search for new antibody markers, for example antibodies directed against HIV regulatory proteins.

AIDS-Related Complex↗

Lymphocyte subsets as surrogate markers in antiretroviral therapy.

Efficacy of antiretroviral treatment is evaluated usually according to reduction of serious events (e.g. opportunistic infections while on therapy) and improvement of survival time. In stages of asymptomatic disease treatment trials have to cover very long time periods to fulfil these requirements. In asymptomatic stages, when viremia is commonly absent, monitoring the host's immune response is an indirect means of measuring antiviral efficacy. CD4+ lymphocyte counts are generally accepted as surrogate in all major trials. The subsets of the CD8+ compartment reflect early and late activation and cytotoxic immune response. CD38+, CD57, CD8+ HLA/DR+ subsets reflect the host's vigorous cellular immune response even in early stages. These subsets are candidate surrogate markers in early and late stages of HIV infection. On the other hand, CD3+ CD4- CD8-, CD19/20 (B lymphocytes) and CD16+ (natural killer cells) do not exhibit any properties of candidate surrogate markers. Established and experimental cellular surrogate markers are discussed including own data and a review of the literature.

Evaluation Studies as Topic↗

Evaluation of saliva as a specimen for monitoring zidovudine therapy in HIV-infected patients.

To facilitate studies of the pharmacokinetic properties of zidovudine, the relationship between plasma and salivary concentrations of the drug was studied, after oral dosage, in 10 HIV-infected patients. Zidovudine concentrations were determined in plasma, unstimulated mixed saliva and citric-acid-stimulated mixed saliva over a period of 3 1/2 hours by high-performance liquid chromatography. Correlation coefficients were r = 0.97 (P less than 0.0001) for stimulated saliva compared with plasma and r = 0.89 (P less than 0.0001) for unstimulated saliva, with average values in unstimulated saliva being 113.8 +/- 44.6% in plasma and 67.8 +/- 25.4% in stimulated saliva. Stimulated saliva values found to be 70% of the total reflected the concentration of the unbound drug in plasma. Except for a shorter half-life time (t1/2) in saliva, pharmacokinetic parameters showed a good correlation in the three types of specimen. These findings and the convenience of sample collection suggest that citric-acid-stimulated saliva might be an appropriate specimen for monitoring zidovudine therapy.

Adult↗

[Electro-ophthalmologic studies in HIV patients].

We examined 44 HIV-positive patients in different disease stages with electroretinogram (ERG), pattern-electroretinogram (PERG), and visually evoked cortical potentials (VECP). Sixty-eight of the 88 eyes examined had a normal fundus and full central vision. Twelve eyes showed cotton-wool ecudates and 8 eyes CMV retinitis. Fifty-four eyes with normal fundus were examined by ERG. Of these 28 (52%) showed marked reduction of the amplitude. In the PERG, 20 eyes out of 50 examined (40%) showed an amplitude reduction. In the VECP, 12 out of 65 eyes (19%) had a reduced amplitude. In the ERG, 7 of 11 eyes (64%) with cotton-wool exudates showed marked pathological findings, as opposed to 4 of 10 cases (40%) in the PERG and 3 of 12 (12%) in the VECP. Seventy-five percent of the eyes with CMV retinitis (6 of 8 cases) showed pathological findings in the ERG and VECP and 100% (all 7 cases examined) in the PERG. These electrophysiological findings suggest that there are diffuse disorders in the retina of HIV-positive patients. It is possible that these findings are based on direct infection of the retina with HIV, or that they represent a vascular disorder, subclinical infection or are related to side effects of the drugs used for the HIV infection.

Adult↗

Non-excretory plasmocytoma--value of imaging procedures.

We report a case of a 84-year old patient with a non-excretory plasmocytoma. Lacking pathological laboratory values, first diagnostic hints on this rare disease were provided by imaging procedures. Computed tomography and plain radiography surpassed bone scan with 99mTc-diphosphonate compounds in detecting bone associated lesions. According to data in the literature, magnetic resonance imaging and bone marrow scintigraphy seem to be useful in quantifying bone marrow involvement, whereas computed tomography and plain radiography appear to be good tools in detecting localized cortical or spongious lesions in multiple myeloma.

Aged↗

Erythrocyte antibodies in AIDS are associated with mycobacteriosis and hypergammaglobulinemia.

Positive direct antiglobulin results prior to transfusion in some of our AIDS patients, as well as some reports in the literature on red cell antibodies in AIDS patients, prompted us to investigate the prevalence of erythrocyte antibodies in AIDS patients with transfusion requiring anemia. In addition we studied the question of relevant correlations with clinical diagnosis and with hematological and immunological laboratory parameters. Of 145 consecutive hospitalized AIDS patients (CDC criteria), 34 (23%) presented with anemia requiring transfusion. With each cross-match a routine antibody screening was performed. In cases of positive reaction additional antibody differentiation was done. Diagnoses, hematologic parameters, and therapy were studied retrospectively. Agglutination was positive in at least one test for 41% (14/34) (group 1). C3d, anti I, cold agglutinins, and IgG occurred most frequently (n = 9/8/7/6 out of 14). Seventy-five per cent (12/14) had leukopenia (less than 4000/microliters), 57% (8/14) had thrombocytopenia (less than 150,000/microliters), and 43% (6/14) showed both. Average values for leukocytes, thrombocytes, and CD4-positive lymphocytes did not differ significantly in patients with (group 1) and without (group 2) erythrocyte antibodies. Average gamma globulin levels were significantly increased in group 1 (23.2 g/l versus 16.9 g/l; p less than 0.001). In group 1, 64% (9/14) had proven mycobacteriosis (6 atypical), in contrast to only 15% (3/20) in group 2 (p less than 0.05). There were no significant differences between the two groups in prevalence of other opportunistic infections, malignant lymphoma, and Kaposi's sarcoma. Autoimmune versus infectious pathogenesis of pathologic erythrocyte antibodies in AIDS has been discussed in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Expansion of activated T lymphocytes (CD3 + HLA/DR +) detectable in early stages of HIV-1 infection.

The phenotypic characterization of lymphocyte subsets in relation to different clinical stages of HIV infection has mainly focussed on CD4 and CD8 cells. Some reports focus on expansion of activated T lymphocytes in AIDS patients. Yet there is no detailed knowledge whether such changes occur also in earlier stages of HIV infection. In order to describe the kinetics and possible pathogenetic meaning of this subset when related to all distinct chronologic stages, we performed two-color flow cytometric lymphocyte differentiation in 173 HIV-infected patients and 30 healthy controls. All subjects were classified according to the Walter Reed (WR) system. Our results show that a significant increase of activated T lymphocytes (CD3 + HLA/DR +) occurs early, in WR1 and WR2, thus preceding the clinically relevant CD4 depletion. This increase is paralleled by an expansion of CD8 + Leu7 + cytotoxic cells. We conclude, that early changes of lymphocyte subsets are detectable in addition to inversion of the CD4/CD8 ratio. The possible pathogenetic meaning including the question of possible autoimmune mechanisms is discussed.

Acquired Immunodeficiency Syndrome↗

Value of 67gallium scintigraphy in primary diagnosis and follow-up of opportunistic pneumonia in patients with AIDS.

Opportunistic pneumonias are a life-threatening complication in patients with AIDS. Early diagnosis and therapy is necessary to improve the prognosis. This study was designed to assess the value of 67gallium scintigraphy in the primary detection and follow-up of these special pneumonias. 67Gallium scintigraphy was performed in 40 patients: 10 normal controls and 30 HIV-positive patients with AIDS or AIDS-related complex (ARC). 67Gallium scan results were compared with current chest x-rays and the results of pathogen detection. The evaluation of positive scans was based on a quantification of the pulmonary uptake, expressed as a pulmonary/soft tissue uptake ratio. Only 8 of 30 patients had a normal scan, while 22 of 30 showed diffuse (13/22) or focal (9/22) increases of pulmonary uptake. In seven of eight patients with normal scans the chest radiograph was negative as well. The one patient with negative scan but positive chest radiograph had pulmonary Kaposi's sarcoma. In 11 of 22 patients, the 67gallium scan and chest x-ray were positive simultaneously. In the other 11 of 22 patients with positive scans, chest radiographs were initially negative but showed pathology in five cases within 1-2 weeks. The reason for positive scans in most cases was an opportunistic lung infection; other forms of pneumonia were observed only in two cases. The defined uptake ratio was demonstrated to be a highly sensitive parameter for monitoring pneumonia and the effects of therapy in follow-up studies. In conclusion, quantitative 67gallium scintigraphy proved to be a reliable and highly sensitive method for primary detection and follow-up of opportunistic pneumonias in patients with AIDS.

AIDS-Related Complex↗

67Ga-scintigraphy for evaluation of AIDS-related intestinal infections.

This study was designed to evaluate the role of 67Ga-scintigraphy in AIDS-related intestinal infections. Seventeen out of twenty-five HIV-positive patients (68%) primarily investigated with 67Ga-scans to screen for opportunistic pneumonia presented pathologic abdominal 67Ga-uptake which was, in most cases, due to proven opportunistic intestinal infection (cytomegalovirus, atypical mycobacteria, cryptosporidiosis etc.). The correlation of abdominal with pulmonary findings has shown that AIDS-related intestinal infections and opportunistic pneumonia may occur concomitantly in the majority cases (11/17). In 6/17 patients positive abdominal findings were observed without opportunistic pneumonia at the same time. Gallium imaging of the abdomen has shown to identify successfully the most common extrapulmonary sites of HIV-related infections. Thus, abdominal imaging or whole body scintigraphy should be a mandatory part of each 67Ga-scan in patients with HIV infection, even if it was primarily performed to screen for opportunistic pneumonia only. Knowledge of multilocular opportunistic infections, usually caused by different pathogens, is clinically important for further diagnostic and therapeutic management.

AIDS-Related Complex↗

Effect of synthetic human glucose-dependent insulinotropic polypeptide (hGIP) on the release of insulin in man.

During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose-dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg-1 min-1 for 30 min and 0.5 pmol kg-1 min-1 for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92 +/- 18 pmol 1(-1) to 257 +/- 42 pmol 1(-1) 60 min after ingestion of glucose (mean +/- SEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 +/- 67 vs. 200 +/- 48 pmol 1(-1); P less than 0.02; 465 +/- 96 vs. 207 +/- 48 pmol 1(-1); P less than 0.01). However, the total and incremental integrated insulin responses during the first 60 min of the study were, though lower, not significantly different from the oGTT experiment when glucose and hGIP were infused simultaneously. Thus, in the presence of mild physiological hyperglycaemia, human GIP is able to enhance the initial insulin response almost equivalently to the stimulus provided by oral glucose. Decreased insulin concentrations during porcine GIP infusions in previous experiments might be due to sequence differences between human and porcine GIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Cryptococcus neoformans meningoencephalitis and multiple infections in AIDS].

A 40-year old homosexual AIDS patient recovering from a Pneumocystis carinii pneumonia developed a Cryptococcus neoformans infection with involvement of the central nervous system (CNS) which could be treated successfully with amphotericin B and flucytosine. After a symptom-free interval of 4 1/2 months, a new acute fatal disease of the CNS did not reveal a cryptococcosis relapse but a necrotizing Toxoplasma encephalitis, a cytomegalovirus infection and striking cultural findings of Staphylococcus aureus in all organs examined. Neither by culture nor by histology Cr. neoformans could be detected in the CNS or in the other organs examined. The temporal course of the Cr. neoformans infection and its specific diagnosis are commented. It is demonstrated that (during or after successful therapy of Pneumocystis carinii pneumonia) a specific cultural examination of specimens from the respiratory tract for Cr. neoformans is needed, in order to recognize a Cr. neoformans infection in its primary stage, i.e. before hematogenous dissemination of Cr. neoformans leading to the secondary stage of the infection.

Acquired Immunodeficiency Syndrome↗

[False-positive test of autonomic neuropathy in HIV infection and AIDS? Case control study of heart rate variability in 62 HIV positive patients].

False positive tests for autonomic neuropathy in HIV-infection and AIDS? Case-control-study of heart rate variation in 62 cases Autonomic neuropathy is said to be common in AIDS. In a cross section study we tested heart rate variability, a simple and sensitive test, in relation to disease severity. The expiratory-inspiratory RR-interval-ratio (RRR) was normal in HIV-infected clinically healthy persons (mean 1.45; n = 10), but progressively lowered in LAS (1.24; n = 12), ARC (1.20; n = 7), AIDS (1.13; n = 20), AIDS with pneumocystis carinii pneumonia (1.07; n = 7) and patients who died within the four month study (1.06; n = 6). The progressive decrease of heart rate variability (from 45% to 6% for group means) is in accord with previous reports. - In a simultaneous case-control study we compared RRR of these 62 patients with those of 62 not HIV infected patients matched for age, sex, resting heart rate and presence of pneumonia. Neither in the six subgroups nor in the total group we found a difference between HIV infected patients and their controls (1.20 +/- 0.18 SD and 1.22 +/- 0.17, respectively; 62 pairs). The decrease of RRR with increasing disease severity in HIV-infected patients was mainly dependent upon increasing heart rate and to a lesser degree upon increasing age. Therefore, a decreased heart rate variability in AIDS is not a specific sign of autonomic neuropathy and likely to be a false positive test result.

Acquired Immunodeficiency Syndrome↗