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J R Bogner

Publications and source records attributed to J R Bogner.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pharmacokinetics of zidovudine after rectal administration in human immunodeficiency virus-infected patients.

We evaluated the pharmacokinetics of rectally administered zidovudine (ZDV) in 10 human immunodeficiency virus-infected adults. After rectal administration of an aqueous ZDV solution (250 mg of ZDV), mean peak ZDV levels were 1.3 +/- 0.7 micromol/liter (mean +/- standard deviation) versus 5.0 +/- 2.2 micromol/liter (P < 0.0001) after oral intake of a 250-mg ZDV capsule. The half-life at beta phase was 87.8 +/- 39.6 min for rectally administered ZDV versus 55.8 +/- 20.1 min (P = 0.035) for orally administered ZDV. The mean area under the concentration-time curve from 0 min to infinity was 232 +/- 181 micromol/liter x min after rectal administration versus 362 +/- 110 micromol/liter x min after oral intake. Although the two routes were not bioequivalent, ZDV was absorbed considerably after rectal administration, with a pharmacokinetic profile resembling that of a sustained-release device.

Administration, Oral↗
PubMed1997

Patterns of mycobacterium avium culture and PCR positivity in immunodeficient HIV-infected patients: progression from localized to systematic disease, German Aids Study Group (GASG/IDKF).

Our aim was to establish the frequency and the longitudinal pattern of MAC culture positivity in late stage HIV-infected patients. Two other aims were to analyse risk factors for progression from localized to systemic disease and the value of PCR diagnosis using blood specimens. A total of 107 patients were recruited to be followed for 32 weeks. Prior MAC treatment and CD4 > 100/microliters were exclusion criteria. A total of 56 patients showed M. avium in at least 1 culture. 10/37 patients with MAC detected by culture first in 'non-sterile' specimens (stool, sputum) and urine progressed to systemic disease as determined by positive blood culture. Risk factors associated with this progression were a high symptom score at baseline, lymphadenopathy, anaemia, and low platelets. PCR was less sensitive than culture in detection of M. avium in blood specimens: Only 7/29 patients with positive blood cultures had a positive PCR at the same time. We conclude that symptomatic patients with advanced HIV-infection have a high frequency of MAC detection. Progression from localized to systemic culture positivity is associated with risk factors. Early 'pre-emptive' therapy is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Single dose, dose-escalating trial with fozivudine tidoxil (BM 21.1290).

BACKGROUND AND OBJECTIVES: In vitro and in vivo experimental data for fozivudine tidoxil [BM21.1290 (FZD) an ether-lipid conjugate of zidovudine] have shown better efficacy, no myelotoxicity and better tolerability compared with zidovudine. Therefore, the objectives of our study were to evaluate the safety of FZD in patients with human immunodeficiency virus (HIV) infection and to establish basic pharmacokinetic data. PATIENTS AND METHODS: In a Phase I dose-escalating trial, seven different single dose applications were studied in 39 patients: 50, 100, 300, 600, 900, 1200 and 1800 mg in capsule and tablet formulations. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. Exclusion criteria were active opportunistic manifestations, concomitant zidovudine therapy and neutropenia (< 750 neutrophils/mm3). Safety parameters, 24 h plasma levels and urinary excretion were determined. RESULTS: The tolerance of FZD was excellent up to single doses of 1800 mg. In only one case, a single episode of loose stool was reproducible in a second treatment period and was therefore considered to be a probable drug-related event. In an amendment to the trial, a tablet formulation of FZD did not induce diarrhoea in this patient. FZD was available in measurable concentrations after 2 to 4 h. Maximum concentrations were reached after 4 to 8 h. After normalization for a dose of 100 mg/patient, the mean AUC was 8.6 mg x h/l and the mean Cmax was 1.13 mg/l; t1/2 was 3.78 h. Interestingly, plasma concentrations of zidovudine and zidovudine glucuronide were much lower than with equimolar zidovudine doses. CONCLUSIONS: The zidovudine conjugate FZD is safe and well tolerated at the seven doses tested. Phase II trials are warranted.

Adult↗
PubMed1997

Phase I/II trial with fozivudine tidoxil (BM 21.1290): a 7 day randomized, placebo-controlled dose-escalating trial.

BACKGROUND AND OBJECTIVES: A Phase I dose-escalating trial with single doses of fozivudine tidoxil (BM21.1290; FZD), in vitro, and experimental in vivo data indicated that further investigations with this compound were warranted. Advantages of fozivudine tidoxil are the direct delivery of zidovudine monophosphate intracellularly and high concentrations in lymphatic tissues. Our objectives were to evaluate safety, tolerability and efficacy of fozivudine tidoxil in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: In a Phase I/II dose-escalating trial, three doses of fozivudine tidoxil (400, 800 or 1200 mg/day) were administered for 1 week. The study was randomized and placebo controlled. Inclusion criteria were HIV infection, CD4 count > 100 cells/mm3 and informed consent. The exclusion criteria were active opportunistic infection and prior antiretroviral treatment. RESULTS: The tolerability of fozivudine tidoxil was excellent in all dose groups. No treatment discontinuations were necessary. Steady-state pharmacokinetics did show slightly higher concentrations as compared with levels after the first dose (20%). Viral load reduction was most pronounced in the 1200 mg/day dose group (-0.64 log). No viral load reduction was seen in the placebo group. CONCLUSIONS: The zidovudine conjugate fozivudine tidoxil is safe and well tolerated at the three doses tested. Based on the differences in molecular weights, the 1200 mg dose is roughly equivalent to 400 mg zidovudine.

Adult↗
PubMed1997

Gastrointestinal lymphomas in patients with AIDS.

Non-Hodgkin-lymphoma (NHL)-most frequently high grade B-cell lymphoma-occurs in 5-10% of individuals with HIV-infection. The gastrointestinal tract (GIT) is the most frequent extranodal site of the disease. The optimal therapy for HIV-related lymphoma remains a matter of controversy. In a retrospective analysis we found gastrointestinal lymphoma in ten of 306 HIV-infected patients (3.3%) with a median CD4-count of 92/microliter at time of diagnosis. Median survival for the chemotherapy treatment group was 15 months. The high incidence of gastrointestinal NHL prompted us to commence a prospective survey on diagnostic procedures, therapy and outcome of patients with HIV-infection and gastrointestinal symptoms. 93 of 341 HIV-infected patients with gastrointestinal symptoms were examined by endoscopy. In selected patients we used in addition endoscopic ultrasound (EUS) for visualization and staging before and after chemotherapy. NHL of the GIT was detected in seven of 93 endoscopically examined patients (7.5%). All patients were treated with CHOP initially. Mean survival time was ten months, mean CD4-count at diagnosis 193/microliter (range 0-417). Our results indicate that the diagnosis of gastrointestinal lymphoma should be considered in any HIV-infected patient presenting with unexplained gastrointestinal symptoms. In this group of patients NHL was detected in 7.5% of cases. The use of EUS improves the staging procedure before therapy. Treatment with CHOP resulted in relatively high remission rates and was associated with a low rate of treatment-induced myelosuppression.

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

[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↗
PubMed1995

[Ultrasound skin findings in HIV infection by imaging with 7.5 MHz linear transducers].

Sonography is an important tool in aiding the diagnosis of tumor-like and cystic findings in the skin and soft tissues. This is also true in patients with HIV infection and AIDS. While sonography of the skin often is performed with 20-MHz transducers, also lower-frequency devices which are more readily available contribute substantially to dermatologic diagnoses. The domain of skin sonography are tumors; in the special context of AIDS, Kaposi's sarcoma and lymphomas are of major interest. The characteristic appearance of Kaposi's tumors is a spindle-shaped outline with low echogenicity and relative homogenicity. The tumor volume is easily established using measurements in two directions. Shrinkage of the volume after therapy, e.g. chemotherapy, may be documented in a more objective manner as compared to subjective rating of nodularity. Several characteristic images of Kaposi's sarcoma, lymphoma, lymph nodes, lipoma, and cysts are demonstrated in the paper.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Differential radiologic diagnosis of HIV-associated lung diseases].

In 1993 in Germany an estimated number of 50,000-70,000 individuals were infected with the human immunodeficiency virus (HIV), WHO estimations ranged up to 14 million HIV-positive individuals including 1 million children. AIDS-related diseases frequently occur in the lung. 65% of all AIDS-defining illnesses begin with life-threatening pulmonary infections. Most frequently HIV-positive patients present with Pneumocystis carinii pneumonia, followed by atypical mycobacteriosis, bacterial infections, Kaposi's sarcoma and non-Hodgkin lymphoma. The purpose of this article is to identify pulmonary HIV-associated diseases by focusing on radiological patterns and correlating them with clinical findings.

AIDS-Related Opportunistic Infections↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1994

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↗