Ganciclovir intraocular device and patient survival.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
F D Goebel
Publications and source records attributed to F D Goebel.
Endothelin-1 immunoreactivity in plasma is elevated in HIV-1 infected patients with retinal microangiopathic syndrome.
Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving blood vessels. HIV-1 related retinal microangiopathic syndrome is a frequent finding in patients with AIDS or AIDS-related complex, presenting predominantly with retinal cotton-wool spots. We investigated 55 HIV-1 infected patients by ophthalmoscopy and for endothelin-1 immunoreactivity in plasma and an additional 76 HIV-1 infected patients only for endothelin-1 levels. For reference values 13 age-matched healthy subjects were studied. In 18 of 55 patients (33%) investigated ophthalmoscopically we found evidence of microangiopathic syndrome. Overall, the mean endothelin-1 immunoreactivity in plasma of HIV-1 infected patients was significantly elevated as compared to controls (4.28 +/- 3.62 versus 2.72 +/- 0.67 fmol/ml, P < 0.0001). HIV-1 infected patients with retinal microangiopathic syndrome had significantly higher plasma levels of endothelin-1 immunoreactivity (4.59 +/- 1.38 fmol/ml) compared to HIV-1 infected patients without microangiopathic syndrome (3.18 +/- 1.64 fmol/ml, P = 0.003). Correlation analysis revealed that endothelin-1 immunoreactivity in plasma had no significant association with disease progression, CD4 cell count, beta 2-microglobulin, neopterin, or age. Endothelin-1 immunoreactivity in plasma was correlated exclusively with retinal microangiopathic syndrome in one or both eyes (r = 0.45, P = 0.0006) and with the number of cotton-wool spots (r = 0.50, P = 0.0001). In conclusion, HIV-1 related retinal microangiopathic syndrome is associated with elevated plasma levels of endothelin-1. By virtue of its potent vasoconstrictor activity endothelin-1 may be involved in the pathogenesis of HIV-1 related vascular disease.
Adult↗
Insulin-dependent diabetes mellitus following pentamidine therapy in a patient with AIDS.
Pentamidine is known to cause severe dysglycaemia by damaging beta-cell function of the pancreas. The exact mechanism still remains unclear. We report the case of a 53-year-old man infected with the human immunodeficiency virus who developed insulin-dependent permanent diabetes mellitus 3 days after starting intravenous treatment with pentamidine for pneumocystis carinii pneumonia. Discharged from hospital the daily need of insulin increased continuously over one year now requiring an average dose of 80 units per day. So far, a number of cases of insulin-dependent diabetes mellitus following pentamidine therapy has been reported, but long-term observations are rare.
AIDS-Related Opportunistic Infections↗
Determination of endothelin-1 immunoreactivity in plasma, cerebrospinal fluid and urine.
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide apparently involved in a number of vascular diseases in man. Nonetheless, its determination in biological samples is difficult, and data on plasma or urine concentrations are controversial. We investigated different sample preparation procedures as well as different radioimmunoassays for their influence on ET-1 measurement. Recovery of ET-1 depended on the extraction procedure, the type and size of the extraction columns and on the biological matrix itself. Incomplete removal of matrix components by the extraction leads to the formation of particulate matter in the evaporated eluate. When dissolved in assay buffer, ET-1 was found to be absorbed to and only partly released from these particulates, so that it was not accessible for measurement in a radioimmunoassay. This was the case for all extraction procedures investigated except for that involving acetic acid. HPLC analysis of spiked samples revealed that ET-1 is in part degraded during extraction, most probably to Meth-sulphoxide ET-1. Dilution curves of synthetic pure ET-1 standards from different suppliers, prepared either in plasma with subsequent extraction or in assay buffer of the respective radioimmunoassay, resulted in considerable differences in the measured values for ET-1-immunoreactivity. Every radioimmunoassay tested had a specific pattern of recognizing different synthetic ET-1 standards. In conclusion, the measurement of ET-1-immunoreactivity is strongly influenced by the experimental conditions of sample preparation as well as by the radioimmunoassay employed.
Absorption↗
Conjunctival microvasculopathy and Kaposi's sarcoma in patients with AIDS.
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AIDS-Related Opportunistic Infections↗
Study of the retinal fiber layer in patients with acquired immunodeficiency syndrome.
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Acquired Immunodeficiency Syndrome↗
Ocular microangiopathic syndrome in patients with acquired immunodeficiency syndrome and its relationship to alterations in cell adhesion and in blood flow.
Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients with 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). Cell adhesion has become an important pathogenetic concept in infectious diseases. We studied 39 patients with AIDS by indirect ophthalmoscopy and by slit-lamp biomicroscopy. Cotton-wool spots were counted as an indicator of retinal microvasculopathy. Conjunctival blood-flow sludging in conjunctival vessels was determined by a standardized rating scale as an indicator of blood-cell adhesion abnormalities. Parameters of immunosystemic damage were determined by fluorescein-activated cell-sorter scan, radioimmunoassay, and enzyme-linked immunosorbent assay. Conjunctival blood-flow sludging was present in 92% of our patients, and cotton-wool spots were observed in 44%. Cotton-wool spots occurred only in patients with significant blood-flow sludging, and the quantity of cotton-wool spots was closely associated with blood-flow sludging (r = 0.64, P < 0.0001). Lower correlations were found between the numbers of cotton-wool spots and the serum level of neopterin (r = 0.40, P = 0.01) or the CD4+ count (r = -0.39, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
[Diagnosis and therapy of gastrointestinal Kaposi's sarcoma in AIDS].
Gastrointestinal Kaposi's sarcoma (KS) is one of the most frequent neoplastic diseases seen in AIDS. Visceral involvement is associated with shorter survival as compared to cutaneous KS. Our aim was therefore to investigate patients with KS endoscopically. In order to improve the early diagnosis of gastrointestinal KS we also employed endoscopic ultrasonographic examinations (EUS). 22 patients recruited for a prospective trial addressing this issue were examined by endoscopy and by EUS. 21 patients had severe cutaneous KS, one patient had no cutaneous KS but showed signs and symptoms of gastrointestinal KS. 15/22 patients (68%) had gastrointestinal KS. Seven patients (32%) had endoscopically normal mucosa. In 2 patients only EUS showed findings suggestive for KS which had not been seen by endoscopy. Follow-up examinations proved typical KS lesions endoscopically in those 2 patients. Using liposomal encapsulated Doxorubicin within a trial (20 mg/m2 intravenously every 3 weeks), we were able to follow 3 patients prior to and during therapy. EUS showed a significant reduction in number and volume of KS lesions as well as a reduction of infiltration depth. In one patient macroscopic and histologic examinations showed complete remission. We conclude that EUS of the upper gastrointestinal tract can be used as a sensitive method for the detection of early gastrointestinal KS. Furthermore, EUS is a method which allows determination of tumor volume and helps in quantification of tumor response after chemotherapy.
Acquired Immunodeficiency Syndrome↗
Retinal detachment in patients with acquired immunodeficiency syndrome.
Cytomegalovirus retinopathy is the most frequent opportunistic infection of the eye in patients with acquired immunodeficiency syndrome (AIDS). We studied 71 patients with cytomegalovirus retinopathy (n = 69) or acute retinal necrosis (n = 2) with respect to the frequency and management of retinal detachment. Retinal detachment was seen in 14 patients (relative frequency, 19.7%). In 2 patients, the retinal detachment was bilateral. In 5 patients, pars plana vitrectomy and silicone-oil tamponade was performed, and in 1 of these patients scleral buckling was applied before vitrectomy. In 3 other patients scleral buckling was performed, and 1 of these individuals had sulfur-hexafluoride injection. In 8 eyes (6 patients), retinal detachment occurred in eyes with completely burned-out retinopathy without relevant function, and no surgical treatment was performed. Long-term retinal reattachment was seen in all 5 patients undergoing pars plana vitrectomy with silicone-oil tamponade. Visual acuity was preserved until the last follow-up in 4 of these 5 patients. In the patients undergoing a buckling procedure alone, no anatomic or functional success was observed. During vitrectomy, reduced retinal vascular perfusion and blood-flow sludging was observed in 2 patients. As the duration of survival of patients with AIDS and cytomegalovirus retinopathy or acute retinal necrosis is increasing, more cases of retinal detachment will be observed. Overall, 5% of patients with AIDS are expected to develop retinal detachment. In conclusion, treatment of cytomegalovirus-associated retinal detachment by pars plana vitrectomy with silicone-oil tamponade seems to be successful and safe and may maintain the patient's quality of life.
AIDS-Related Opportunistic Infections↗
Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma.
Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to conventional combination therapy is underway.
AIDS-Related Opportunistic Infections↗
HIV-related ocular microangiopathic syndrome and color contrast sensitivity.
PURPOSE: Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. METHODS: A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton-wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). RESULTS: The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CONCLUSION: CCS deficits in patients with HIV disease are primarily associated with the number of cotton-wool spots. Results of this study are in accordance with the hypothesis that CCS deficits are in a relevant part caused by neuroretinal damage secondary to HIV-related microangiopathy.
Acquired Immunodeficiency Syndrome↗
[Acute kidney failure caused by sulfadiazine stones. A complication of the therapy of toxoplasmosis in AIDS].
A 45-year-old man with AIDS was treated for a recurrence of cerebral toxoplasmosis with sulphadiazine, 4 g, and pyrimethamine, 75 mg, daily. Owing to a lack of appetite and dysphagia he drank rather little water during the first week of treatment. On the 13th day after starting the drugs he had bilateral renal colics and renal failure was diagnosed (serum creatinine 3.8 mg/dl). Ultrasound examination demonstrated multiple stones with bilateral urinary retention. After parenteral fluid replacement, alkalization of the urine with sodium-potassium-hydrogen citrate and N-butylcopolamine a stone, consisting of sulphadiazine and acetylsulphadiazine, was passed after two days. Three days later the creatinine concentration was within normal limits, and in further two days the ultrasound picture was normal. It is pointed out that diarrhoea, fever or dysphagia often prevent sufficient fluid intake in AIDS patients. Satisfactory oral fluid intake and alkalization of urine is thus of great importance for avoiding complications during sulphadiazine treatment.
AIDS-Related Opportunistic Infections↗
Zidovudine in persons with asymptomatic HIV infection and CD4+ cell counts greater than 400 per cubic millimeter. The European-Australian Collaborative Group.
BACKGROUND: Zidovudine therapy is of benefit in the treatment of symptomatic and asymptomatic human immunodeficiency virus (HIV) infection in persons with CD4+ cell counts of less than 500 per cubic millimeter. The efficacy, safety, and duration of benefit of zidovudine in those with 500 or more CD4+ cells per cubic millimeter are uncertain. METHODS: In a double-blind, placebo-controlled trial, 993 patients with asymptomatic HIV infection and CD4+ cell counts above 400 per cubic millimeter were randomly assigned to receive zidovudine (500 mg twice daily) or placebo for three years. The primary end point was progression of disease, as defined by the development of Centers for Disease Control and Prevention (CDC) group IV disease (including recurrent oral candidiasis, hairy leukoplakia, or progressive diarrhea) or two CD4+ cell counts below 350 per cubic millimeter. This outcome measure was changed from the original end point of the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex to reflect changes in recommendations for management. The study was terminated after the first interim analysis. RESULTS: Disease progression was significantly less frequent in the zidovudine group (relative risk, 0.56; 95 percent confidence interval, 0.43 to 0.75; P < 0.001 by the log-rank test). The probability of disease progression at two years was 0.19 with zidovudine, as compared with 0.34 with placebo (95 percent confidence interval for the difference, -0.21 to -0.08). Progression to CDC group IV disease was reduced by half in the zidovudine recipients (relative risk, 0.49; P = 0.049) and decline in CD4+ cell counts to below 350 per cubic millimeter was reduced by 40 percent (relative risk, 0.60; P < 0.001). The inclusion of early HIV disease events (oral candidiasis, oral hairy leukoplakia, and herpes zoster) as end points confirmed the effects of zidovudine on the progression of clinical disease (relative risk, 0.55; 95 percent confidence interval, 0.37 to 0.84; P = 0.004). The median duration of treatment was 94 weeks. Severe hematologic or clinical side effects were rare. CONCLUSIONS: Treatment with zidovudine benefits HIV-infected persons with CD4+ cell counts above 400 per cubic millimeter. Despite the use of doses larger than those now generally prescribed, zidovudine was well tolerated for up to three years by most of our patients.
AIDS-Related Complex↗
Potent stimulation of monocytic endothelin-1 production by HIV-1 glycoprotein 120.
Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex.
AIDS Dementia Complex↗
[Prevention in the HIV-infected].
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AIDS-Related Opportunistic Infections↗
Reduction of HIV-1 antigen production by phosphatidylcholine containing formulations via growth inhibition of HIV-1-infected cells.
Phosphatidylcholine (PC) and licensed formulations containing PC were tested for their influence on the proliferation and viability of cells permanently infected with HIV-1 (human immunodeficiency virus type 1). PC alone, as well as pharmaceutical formulations containing PC, selectively inhibited the growth of productively infected lymphoid cells. The strongest growth inhibition was observed with formulations containing PC, glycerol and triglyceride together. The growth inhibition was dose-dependent for HIV-1-infected cells. Additionally, PC-containing formulations dramatically reduced antigen production from peripheral blood mononuclear cells (PBMCs) infected in vitro with HIV-1. In vivo experiments with Rauscher-MuLV-infected mice showed that PC administered either intraperitoneally or orally was able to inhibit Rauscher-virus-induced splenomegaly. PC-containing formulations are currently used in man for supportive therapy at doses, which in vitro induced 50% growth inhibition of HIV-1-infected cells in vitro. Such doses have been used in man without side effects for many years. Thus, PC-containing formulations may be valuable for the treatment of HIV-1-infected individuals.
Animals↗
Ultrasound as a tool to evaluate remission of cutaneous Kaposi's sarcoma.
OBJECTIVE: To evaluate ultrasound measurement of Kaposi's sarcoma (KS) tumour volume for follow-up during therapy. Two-dimensional evaluation of size and description of gross alteration (for example, colour, nodularity, resolution) was used to assess treatment of KS. Flattening of palpable cutaneous KS lesions during anti-KS therapy has not been quantified objectively by a reliable method. METHODS: In six patients with advanced AIDS and KS, a total of 17 cutaneous lesions were evaluated prospectively by ultrasound and surface measurements. KS lesions were examined histologically before and after 12 weeks of chemotherapy with liposomal doxorubicin. RESULTS: In comparison with size reduction, volume measurement showed a more pronounced reduction of tumour volume. The mean tumour volume was reduced by 94% from 451 mm3 +/- 655 mm3 to 66 mm3 +/- 165 mm3 at week 12 (P < 0.001). Histological evaluation of lesions no longer detectable by ultrasound after therapy showed abundant siderophages but no increase in spindle cells and no mitoses. CONCLUSIONS: Our findings suggest that ultrasound is a useful method with which to follow growth and remission of cutaneous KS. In contrast, pigmentation due to iron deposition is unaffected by chemotherapy because, despite histological remission, pigmentation can persist. Though ultrasound cannot replace histologic evaluation for complete response, we suggest the use of ultrasound assessment, thus introducing a more objective criterion than subjective rating of nodularity.
Adult↗
Brain HMPAO-SPECT and ocular microangiopathic syndrome in HIV-1-infected patients.
OBJECTIVE: The pathogenesis of neurologic and neuropsychologic dysfunction in HIV-1 infection is unclear. The purpose of the study was to determine an association between cerebral perfusion and HIV-1-related ocular microangiopathic syndrome. METHODS: We studied 28 HIV-1-infected patients, seven of whom presented with asymptomatic HIV infection, nine with lymphadenopathy syndrome or AIDS-related complex, and 12 with AIDS. Cerebral perfusion was semi-quantitatively measured by single photon emission computed tomography of the brain using technetium-99 hexamethyl-propylenamine oxime (HMPAO-SPECT). The conjunctival manifestation of HIV-1-related microangiopathic syndrome was measured by a rating scale determining blood-flow sludging and, retinal cotton-wool spots were counted. CD4 count, neopterin, beta 2-microglobulin (beta 2M), haemoglobin, and age were determined as putative confounding variables. RESULTS: Mean conjunctival sludge in patients with normal HMPAO-SPECT findings was 1.3 +/- 0.5 (mean +/- s.e.m.); no cotton-wool spots were present. In patients with slightly impaired HMPAO-SPECT, it was 2.1 +/- 0.6 and mean cotton-wool spot count was 1.1 +/- 0.4. In patients with severely impaired HMPAO-SPECT, mean conjunctival sludge was 4.5 +/- 0.3 and mean cotton-wool spot count was 4.9 +/- 1.1 HMPAO-SPECT findings were closely associated with conjunctival sludge (r = 0.72; P < 0.001) and number of cotton-wool spots (r = 0.78; P < 0.001), whereas only a slight association with staging of HIV disease was found (P = 0.052). Analysis of covariance controlling for CD4 count neopterin, beta 2M, age, and haemoglobin demonstrated a significant difference between the three HMPAO-SPECT groups for both the number of cotton-wool spots (P < 0.001) and the conjunctival sludge rating (P < 0.001). CONCLUSION: There was a close association between severity of HIV-1-related ocular microangiopathic syndrome and severity of cerebral hypoperfusion. Microvascular alterations might contribute to the pathogenesis of neurological and neuropsychological symptoms in patients with HIV-1 disease. Furthermore, the conjunctival sludge rating and the number of cotton-wool spots might be appropriate indicators for severity of microvascular changes of the central nervous system [corrected].
AIDS-Related Complex↗