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Biomedical subjects

A Rieger

Publications and source records attributed to A Rieger.

At least 19 recordsLinked to original sources

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects.

To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat-derived factor retinol-binding protein-4 (RBP-4) in HIV-infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Fourteen HIV-positive, HAART-naïve subjects were compared with 10 HIV-negative healthy controls and reassessed after a 1-year treatment with HAART. Plasma visfatin and RBP-4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X-ray absorptiometry (DXA). Homeostasis model assessment (HOMA-IR) was assessed using insulin and glucose levels. Visfatin and RBP-4 levels in HIV-positive subjects were comparable with those of HIV-negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6.9-fold and 7.1-fold increase of visfatin and RBP-4 levels (+54.0 +/- 9.7 ng mL(-1), P < 0.0001 and +95.3 +/- 31.7 ng mL(-1), P < 0.01), respectively. Leptin (-2.7 +/- 1.6 ng mL(-1), P = 0.054) was unchanged and adiponectin (-2.8 +/- 0.7 microg mL(-1), P < 0.01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP-4 (r = 0.78, P = 0.001), fat-free mass (FFM, r = 0.75, P < 0.05) and change of HOMA-IR (r = 0.64, P < 0.05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Treatment with HAART induced a pronounced increase of plasma visfatin and RBP-4 as well as a decrease of adiponectin in HIV-infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.

Adiponectin↗

Local and systemic hemorheological effects of cerebral hyper- and hypoperfusion in a porcine model.

Using a well defined pig model, we investigated whether cerebral hypertension and hypotension influence hemorheological factors. After surgical preparation and stabilization, periods of hyperventilation, controlled periods of cerebral perfusion pressure increases and decreases were utilized. After each period, blood samples were collected from the cannulated femoral artery and vein, and from the superior sagittal sinus. Erythrocyte deformability, whole blood and plasma viscosity and hematological parameters were determined. Erythrocyte deformability significantly worsened in arterial samples after hypertension and hypotension, and in sinus samples it was impaired after hypotension period. Hematocrit significantly increased in arterial and sinus samples during hypertensive period, accompanied by similar alterations in whole blood viscosity. We conclude that hemodynamic changes caused by hyperventilation, hyper- or hypotension can influence hemorheological factors, and suggest that the rheological alterations can affect local hemodynamic and metabolic conditions.

Analysis of Variance↗

Brain tissue oxygen monitoring for assessment of autoregulation: preliminary results suggest a new hypothesis.

Brain tissue oxygen monitoring (P(ti)O2 (Neurotrend, Codman, Germany) was employed in addition to standard intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in seven patients with severe neuronal damage of heterogeneous etiology. The correlation between P(ti)O2 changes and CPP fluctuations during periods of 30 minutes were analyzed, when CPP was above 70 mmHg and lower than 100 mmHg. A new ratio, the CPP-oxygen-reactivity (COR) index was calculated as COR=delta p(ti)O2 %/delta CPP%. The patient COR values were compared to those found in the brain of six noninjured anesthetized piglets. The analysis was performed to determine the significance of synchronous fluctuations of CPP and P(ti)O2, when CPP is above the lower threshold of autoregulation. The correlation between CPP variations and p(ti)O2 variations was found to be strong (R(mean)) = 0.74 +/- 0.17) in the patients and was weak in the uninjured animals (R(mean)) =0.38 +/- 0.43). The COR (mean) was 2.05 +/- 0.57 in patients and 0.78 +/- 0.6 in the animals. In the injured brain of our patients, we observed an unexpectedly close correlation between P(ti)O2 and CPP variations when CPP levels were within a therapeutically targeted range (70 to 100 mmHg). In a porcine model, we could not find this relationship in the noninjured brain. We speculate that an increased COR might be indicative for an impaired local pressure autoregulation. The preliminary data suggest that COR values above "1" might be pathologic. However, the reported sample sizes are too small to provide sufficient statistical power to justify inferential statistical analyses. As such, results are presented with descriptive statistics only, and should be regarded as a hypothesis.

Algorithms↗

Successful treatment of an aciclovir-resistant herpes simplex type 2 infection with cidofovir in an AIDS patient.

Management of the increasing frequency of aciclovir-resistant herpes simplex virus (HSV) infections among immunocompromised human immunodeficiency virus-infected people demands additional treatment options. We report the case of a 38-year-old patient with acquired immune deficiency syndrome who suffered from a perianal butterfly ulcer, which was HSV-2 positive by polymerase chain reaction (PCR) analysis. The ulcer appeared during treatment of a cytomegalovirus (CMV) pneumonitis with ganciclovir. Despite additional valaciclovir therapy the lesion gradually progressed in size. Investigations including histology, PCR analysis and in situ hybridization of a biopsy from the growing ulcer margin confirmed the presence of HSV-2 infection. Importantly, HSV isolates from this specimen were resistant to aciclovir. Based on a report about the successful treatment of aciclovir-resistant HSV infection with cidofovir, our patient received this drug intravenously at a dose of 5 mg kg-1 body weight once weekly for a total of 3 weeks. Concomitant oral probenecid and prehydration were administered to minimize nephrotoxicity. Within 30 days of treatment the ulcer had almost (> 95%) completely healed. We conclude that cidofovir is a potent antiviral drug with a potential usefulness in the treatment of aciclovir-resistant HSV-2 infection. It deserves further investigation in clinical trials.

AIDS-Related Opportunistic Infections↗

Olfactory function in HIV-positive subjects.

The aim of this study was to reinvestigate previous reports of chemosensory dysfunction in HIV-positive subjects. Odor thresholds, odor discrimination and odor identification were assessed using the Sniffin' Sticks test battery. Seventy-four HIV-positive patients were tested. According to CDC criteria, 38 subjects were classified as stage A, 10 as stage B and 26 as stage C. None of the subjects exhibited severe cognitive impairment. Compared to normative data all subjects had normal odor identification and discrimination. However, odor thresholds were well below the median of a normal population. There were no significant differences between stage A, B or C subjects. This may be interpreted as indicating that olfactory dysfunction is among the primary deficits of HIV infection and occurs independently of disease stage. These results confirm previous work suggesting that odor thresholds are elevated early in HIV infection whereas a decline in identification and discrimination abilities is correlated with reduced cognitive abilities.

AIDS-Related Opportunistic Infections↗

Sex differences in HAART-associated dyslipidaemia.

OBJECTIVES: Because female sex protects against dyslipidaemia and atherosclerosis in normal subjects, we aimed to reveal potential sex differences in metabolic side-effects of a newly initiated highly active antiretroviral therapy (HAART) regimen, and to relate these changes to endothelial cell activation as measured by levels of circulating E-selectin (cE-selectin). DESIGN: Prospective longitudinal cohort study. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive male (n = 27) and female patients (n = 13) with a plasma viral load of > or = 10 000 copies/ml and 35 healthy controls were enrolled in the study. All participants were weight stable, free of acute opportunistic infections, and had not taken any protease inhibitors before. Serum levels of lipids, insulin, leptin, and cE-selectin were measured before initiation of HAART, and at 3 and 6 months thereafter. RESULTS: HAART increased serum levels of triglycerides, leptin, and low-density lipoprotein (LDL) cholesterol; these effects were more distinct in women. Fasting insulin levels and the LDL : high density lipoprotein (HDL) ratio increased only in female HIV-infected patients (P < 0.02 versus men). In contrast, endothelial activation, as measured by cE-selectin, decreased more in men (P < 0.02) than in women. As a consequence, women had higher triglycerides and leptin levels after therapy than did men, and the LDL : HDL ratio and cE-selectin levels, which were initially higher in men, were no longer different between the sexes. CONCLUSIONS: Metabolic adverse effects during HAART are more pronounced in women than in men. Hence, female HIV-infected patients seem to loose part of their natural protection from atherosclerosis during antiretroviral therapy.

Adult↗

Primary central nervous system lymphoma in AIDS: a wider spectrum of CT and MRI findings.

Diagnosis of primary central nervous system lymphoma (PCNSL) in patients with AIDS based on radiological findings is still a challenging problem. Our purpose was to review the CT and MRI findings in PCNSL in our patients with AIDS and compare them with those reported in the literature. CT and MRI of 28 patients with AIDS and pathologically confirmed PCNSL were analysed retrospectively for the number of lesions, their site, size, density, signal intensity, contrast enhancement, oedema and mass effect. We found 82 lesions. On CT 45 lesions were found in 22 patients, whereas MRI revealed 66 in 20 patients. The lymphoma was solitary in 20 patients (29 %) and multiple in 20 (71%). Spontaneous haemorrhage was seen in 7 patients. Contrast-enhanced MRI showed no enhancement in 27.3 % (18/66) of the lesions. In one patient diffuse signal abnormalities in the white matter were seen on T2-weighted images. Our findings suggest that the previously described spectrum imaging characteristics of PCNSL has widened. Neuroradiologists should be aware of the variable appearance in patients with AIDS. Spontaneous haemorrhage, a non-enhancing lesion, or diffuse white matter changes do not exclude lymphoma in an immunocompromised patient.

Adult↗

Ocular blood flow in patients infected with human immunodeficiency virus.

PURPOSE: Alterations of ocular blood flow may play a role in the pathophysiology of human immunodeficiency virus (HIV) related retinal microvasculopathy. In this study ocular blood flow was investigated in patients with HIV infection. DESIGN: In a prospective, cross-sectional study ocular blood flow was measured in 37 eyes of consecutive HIV- infected persons and compared with the data of age-matched healthy controls. This sample size was calculated based on an alpha-error of 0.5 and a beta-error of 0.8. METHODS: Macular white blood cell flow, fundus pulsation amplitude, and blood flow velocities in the retrobulbar vessels were measured with blue field entoptic technique, laser interferometry, and Doppler sonography, respectively. Immunologic and ophthalmologic status was evaluated from each patient. RESULTS: Mean CD4+ cell count of the HIV-infected persons was 206.8 +/- 145.6 cells/mm(3). In five patients HIV-related retinopathy was observed. A significant reduction in leukocyte density was seen in HIV infected persons (82.2 +/- 23.4) as compared with the control group (102.0 +/- 28.4; P =.019). The resistive index in the central retinal artery was higher in HIV infected patients (0.77 +/- 0.05) as compared with the controls (0.74 +/- 0.04; P =.04). The other hemodynamic parameters were not different between groups. No correlation of flow parameters and CD4+ cell count or HIV-related retinopathy was observed. CONCLUSIONS: Decreased macular leukocyte density was detected in HIV infected persons. Our study suggests that abnormal retinal hemodynamics in individuals infected with HIV may be involved in the pathogenesis of HIV-related microvasculopathy.

Adult↗

Highly active antiretroviral therapy responders exhibit a phenotypic lymphocyte pattern comparable to that of long-term nonprogressors.

BACKGROUND: The implementation of highly active antiretroviral therapy (HAART) in patients with progressive HIV-1 disease has resulted in a marked reduction of HIV-1-associated morbidity and mortality. In fact, the risk of HAART responders to develop opportunistic infections becomes similar to that of long-term nonprogressors (LTNPs). METHODS: Reasoning that HAART may ultimately have consequences on both the quantity and quality of immune responses of a HIV-1-infected person, we assessed CD4+ and CD8+ T cell subsets in HAART recipients over a time period of 15 months and compared them to the lymphocyte phenotype of LTNPs and healthy controls. Evaluations included quantitative determinations of memory (CD45RO+CD62L-), naive (CD45RO-CD62L+), effector (CD27-, CD28-) and activated (HLA-DR+, CD38+, CD95+) CD4+ and CD8+ lymphocytes. The T cell function was assayed by skin tests. RESULTS: Compared to healthy persons, treatment-naive patients with progressive disease exhibited a considerable reduction of CD4+ T cells with many of the remaining T cells showing signs of activation at baseline. CD8+ T cells were greatly increased in number, mainly because of an expansion of CD28- effector and memory CD8+ T cells. LTNPs, in contrast, had stable CD4+ and elevated CD8+ T cell counts, the latter being mainly due to a marked increase in CD27- effector cells. Essentially, the same immunophenotype was seen in HAART responders after 15 months of treatment when compared to LTNPs. CONCLUSIONS: It is tempting to speculate that a HAART-induced reduction in viral load may influence the immune system's capacity to mount protective responses to pathogenic microorganisms.

Acquired Immunodeficiency Syndrome↗

Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy.

BACKGROUND AND PURPOSE: Recent studies have shown the beneficial effect of highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencephalopathy (PML). The purpose of our study was to evaluate the initial and follow-up imaging findings and survival in patients with PML who were treated with HAART. METHODS: The clinical course and MR imaging findings on initial and follow-up MR studies in four consecutive AIDS patients with PML who were treated with HAART are described. RESULTS: Two patients were short-term survivors and died after 3 months. Two patients are still alive, with a survival time of 22 and 43 months, respectively. On initial MR studies, more extensive white matter changes were seen in the short-term survivors. Development of a mass effect and temporary enhancement (in one patient) was observed in two HAART responders on follow-up MR studies. Increased hypointensity on T1-weighted images with concomitant low signal on fluid-attenuated inversion-recovery fast spin-echo (FLAIR-FSE) images was seen in two responders, representing leukomalacia. Atrophic changes of the involved areas of the brain, consistent with burnt out PML lesions, were seen in two long-term survivors. In the short-term survivors, increased hypointensity was present on T1-weighted images with increased high signal on FLAIR-FSE images, representing progressive destructive disease. CONCLUSION: Our results suggest that a clinical and radiologic response can be seen in some patients with AIDS-associated PML on HAART while in others there may be no beneficial response. Development of a mass effect and temporary enhancement on MR images in the early phase of treatment might represent positive predictive factors for prolonged survival.

Acquired Immunodeficiency Syndrome↗

[Cerebral oxygen reactivity determination--a simple test with potential prognostic relevance].

UNLABELLED: Brain tissue oximetry (ptiO2) using flexible micro-polarographic electrodes is a loco-regional approach to monitor oxygen supply to the injured brain, after neuronal damage. In patients after severe head injury (SHI), disturbances of CBF and CO2 related vasoconstriction have been demonstrated. CO2 reactivity testing may assist to determine outcome in these patients. Not much information is available on the preservation of vasoreactivity to arterial hyperoxia after neuronal damage. Therefore, we studied the response of ptiO2 in 7 piglets and in 14 patients on day one after trauma to 100% FiO2 ventilation (O2rea) and analyzed the 3 month outcome using the Glasgow-Outcome-Score (GOS). In the animal study, we placed a Paratrend 7 (P7) sensor for ptiO2 measurements in the non injured frontal white matter. The animals were anesthetized and mechanically ventilated. FiO2 was increased from 30 (+/- 5)% to 100% over a period of 5 minutes. In patients, we placed the P7 probe in the frontal lobe. FiO2 was increased from 35 (+/- 5)% to 100% over a period of 6 hours. O2rea was tested by calculating the percentage change of ptiO2 during 100% FiO2 ventilation, compared to the baseline value of 35% FiO2. By analyzing the patient outcome, we were able to define two patient populations according to the GOS at three month (Group I: favorable outcome [GOS 0-2]; Group II: poor outcome [GOS 3-4]). For the non-injured brain tissue in animals were revealed an O2rea = 0.21 (+/- 0.12). PATIENTS: Group I: O2rea = 0.4 (+/- 0.16); Group II: 0.9 (+/- 0.6). Group I and II were statistical significant different (p < 0.05; unpaired t-test). Oxygen reactivity in severely head patients is a simple test with prognostic value using ptiO2 measurement. These results may be explained by the close relationship of CBF disturbances to oxygen vasoreactivity after traumatic brain injury. The O2rea in animals without neuronal damage is smaller than in patients after SHI. We speculate, the animal data could be considered as normal value of O2rea in non injured brain tissue.

Adolescent↗

Endoscopic third ventriculostomy is the treatment of choice for obstructive hydrocephalus due to pediatric pineal tumors.

Pineal lesions in the pediatric patient are often complicated by the development of hydrocephalus due to obstruction of the aqueduct or the third ventricle by tumor masses. In such cases, hydrocephalus treatment has the highest priority and should be performed prior to any surgical treatment of the pineal tumor itself. The golden standard in obstructive hydrocephalus treatment remains placement of a temporary or permanent cerebrospinal fluid shunt, although there are many long-term complications associated with a shunt system. To avoid these and to render the patients independent from a failure-prone shunt system, we employed endoscopic third ventriculostomy for permanent relief of elevated intracranial pressure prior to surgical removal of the pineal lesions. The present study summarizes the results of this approach in 7 pediatric patients with obstructive hydrocephalus. No complications of the endoscopic procedure were encountered, and the ventriculostomy remained patent in all cases, as confirmed by motion sensitive MRI. The advantages of endoscopic third ventriculostomy as compared with other techniques are discussed, and its increasing role in the management of children with space occupying lesions of the pineal region is defined.

Adolescent↗

Cerebrovenous blood temperature-influence of cerebral perfusion pressure changes and hyperventilation: evaluation in a porcine study and in man.

The objective of the first part of this study was to use an animal model to investigate the relationship between temperature in the cerebrovenous compartment and cerebral perfusion pressure. In the second part of the study, the objective was to examine the influence of hyperventilation and hypothermia on jugular bulb temperature and body temperature in patients undergoing elective neurosurgery. Intracranial pressure was increased artificially by inflating an infratentorial supracerebellar placed balloon catheter in nine pigs under general anesthesia. Temperature was monitored by thermocouples inserted in the sagittal sinus, white matter of the left lobe and abdominal aorta during the ensuing decrease in cerebral profusion pressure (CPP). Cerebrovenous blood temperature (jugular bulb) and body temperature (urinary bladder) were simultaneously monitored in 24 patients undergoing craniotomy. Moderate hyperventilation was performed in all patients. Cerebrovenous blood and core body temperature were recorded and differences between these two temperatures calculated at the beginning and the end of hyperventilation. At the beginning of the intracranial pressure (ICP), increase mean temperatures of cerebrovenous blood and cerebral tissue (left lobe) were lower than core body temperature. During CPP reduction the difference between core body temperature and cerebrovenous blood temperature increased significantly from 0.86+/-0.44 degrees C prior to ICP rise to 1.19+/-0.58 degrees C at maximum ICP. Before hyperventilation, cerebrovenous blood temperature was higher in 19 patients (+/- difference: 0.34 degrees C +/- 0.27) and equal or lower in five patients (difference: -0.08 degrees C +/- 0.11), than core body temperature. At the end of hyperventilation, the difference between cerebrovenous blood temperature and core body temperature increased (+0.42 degrees C +/- 0.24) in those 19 patients who had started with a higher cerebrovenous blood temperature and decreased (-0.10 degrees C +/- 0. 18) in the other five patients. Both studies demonstrated that the temperature of cerebrovenous blood is influenced by maneuvers which are supposed to decrease cerebral blood flow.

Adult↗

Highly active antiretroviral therapy for patients with AIDS dementia complex: effect on MR imaging findings and clinical course.

BACKGROUND AND PURPOSE: Recent studies have reported the clinical improvement in patients with AIDS treated with a combination of antiretroviral regimens. The purpose of our study was to describe the effects of highly active antiretroviral therapy on MR images in patients with HIV encephalopathy and to compare the clinical course with follow-up neuroimaging studies. METHODS: Initial and follow-up MR imaging findings are described in four patients with AIDS dementia complex at baseline and after antiretroviral therapy, and correlated with clinical and immunologic findings. RESULTS: Initial MR imaging revealed white matter signal abnormalities on long-TR images without mass effect and without enhancement on postcontrast images, consistent with HIV encephalopathy. Lesions were located in the basal ganglia and posterior fossa in two patients. All four patients showed progression of white matter disease on the first follow-up MR scan (mean, 6 months). On subsequent scans, regression was seen in three patients and stabilization of white matter disease was observed in one patient. Increases in CD4+ count and decreases in viral load below the limit of quantification were present in all patients. CONCLUSION: Although our patient population was small, the results suggest that disease regression in patients with AIDS dementia complex after treatment with highly active antiretroviral therapy can be characterized and monitored by MR imaging.

AIDS Dementia Complex↗