Renal blood flow measurement by positron emission tomography using 15O-labeled water

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.     

Pathophysiology of Parkinson's disease: Mitochondria,alpha-synuclein and much more…

Parkinson's disease (PD) is a complex, age-related, neurodegenerative disease whose pathogenesis remains incompletely understood. Here, we give an overview of the progress that has been made over the past four decades in our understanding of this disorder. We review the role of mitochondria, environmental toxicants, alpha-synuclein and neuroinflammation in the development of PD. We also discuss more recent data from genetics, which strongly support the endosomal-lysosomal pathways and mitophagy as being central to PD. Finally, we discuss the emerging role of the gut-brain axis as a modulator of PD progression. This article is intended to provide a comprehensive, general and practical review of PD pathogenesis for the general neurologist.     

Hemoglobin sickle cell disease complications: a clinical study of 179 cases

Background

Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease.

Design and Methods

The study involved a single center series of 179 patients. Clinical and biological data were collected with special attention to the assessment of pulmonary arterial hypertension and nephropathy.

Results

Hemoglobin sickle cell diagnosis was delayed and performed in adulthood in 29% of cases. Prevalence of hospitalized painful vasoocclusive crisis, acute chest syndrome and priapism was 36%, 20% and 20%, respectively. The most common chronic organ complications were retinopathy and sensorineural otological disorders in 70% and 29% of cases. Indeed, prevalence of complications reported in homozygous sickle cell disease, such as nephropathy, suspicion of pulmonary hypertension, strokes and leg ulcers was rather low (13%, 4% and 1%, respectively). Phlebotomy performed in 36% of this population (baseline hemoglobin 11.5 g/dL) prevented recurrence of acute events in 71% of cases.

Conclusions

Our data suggest that hemoglobin sickle cell disease should not be considered as a mild form of sickle cell anemia but as a separate disease with a special emphasis on viscosity-associated otological and ophthalmological disorders, and with a low prevalence of vasculopathy (strokes, pulmonary hypertension, ulcers and nephropathy). Phlebotomy was useful in reducing acute events and a wider use of this procedure should be further investigated.     

Rifabutin prophylaxis against Mycobacterium avium complex infections in HIV-infected patients: impact on the incidence of campylobacteriosis

Following the observation of the decreasing occurrence of campylobacteriosis in HIV-infected patients. This study examines the incidence of campylobacteriosis in patients who had received rifabutin prophylaxis against Mycobacterium avium complex (MAC) infection compared with the incidence observed among patients treated before the advent of rifabutin. A retrospective analysis (February 1992 to November 1995) was conducted in a hospital HIV inpatient unit. The study included two patient groups: 73 HIV-infected patients with CD4 counts of < 100 cells/microL (mean 30 cells/microL) who were treated between February 1992 and July 1993 and who had not received rifabutin prophylaxis (Group R-), as well as 90 HIV-infected patients with CD4 counts of < 100 cells/microL (mean 22 cells/microL) who had received rifabutin 300 mg/day as primary prophylaxis against MAC bacteremia between July 1993 and November 1995 (Group R+). For the patient population as a whole, 20 episodes of campylobacter infection were observed in 13 patients. Causative pathogens were Campylobacter jejuni (n = 10), C. coli (8), and unidentifiable (2). Seventeen episodes (in 12 patients) of campylobacter infection occurred in Group R- versus 3 episodes (in 2 patients) in Group R+ (p < 0.0005). The rate of symptomatic infection per 100 patient-months was 0.251 in Group R+ versus 2.02 in Group R-. The results of this study indicate that rifabutin prophylaxis was associated with a decrease in the rate of campylobacter infection in HIV-infected patients. These findings are supported by evidence that rifabutin is active against C. jejuni in vitro.     

Comparison of PET with radioactive microspheres to assess pulmonary blood flow.

Microsphere technique is the reference for assessment of pulmonary blood flow (PBF) but is destructive; PET, however, can determine PBF noninvasively. Comparisons of these 2 methods are scanty. Our study aimed at comparing these 2 techniques using a mathematic model taking into account the right ventricle in determining the transit time of a tracer through lung tissue. METHODS: Ten normal pigs were investigated at baseline, during dobutamine infusion, and during 10 cm H(2)O of positive end-expiratory pressure. Under each condition, PBF was successively measured with PET (PET-PBF) and radioactive microspheres (MS-PBF). For PET-PBF, 2 mCi (74 MBq) (15)O-labeled water were injected intravenously over 20 s and PET scanning was performed for 10 min. The input function was determined noninvasively from PET and invasively from mixed venous blood withdrawals. PET-PBF was computed using a mathematic model taking into account the right ventricle in determining the transit time of the tracer through lung tissue. For MS-PBF, 1 given isotope was injected under a given condition. PET-PBF and MS-PBF for 5 lung regions were compared. RESULTS: PET-PBF significantly correlated with MS-PBF both over all experimental points (PET-PBF = 0.79. MS-PBF + 1,538; r = 0.79; P < 0.001) and in separate lung regions. Invasive and noninvasive input functions also correlated significantly (r = 0.90; P < 0.001). Simulations stressed the crucial role of the right ventricle to the transit time of tracer through lung tissue in the determination of PET-PBF. CONCLUSION: PBF can accurately be assessed using PET and a mathematic model taking into account the right ventricle in determining the transit time of a tracer through lung tissue. Noninvasive determination of the input function of the right ventricle is accurate and can readily be used for clinical applications.     

Paranoid induction reduces N400s of healthy subjects with delusional-like ideation

A previous study suggests that the amplitude of the N400 event-related potentials (ERPs) of healthy subjects does not vary with their delusional-like ideations. This contrasts with the smaller N400 amplitudes observed in more- than in less-deluded schizophrenia patients. Here, we hypothesize that these smaller N400 amplitudes were related to the paranoid feelings patients had during the ERP recording. We thus induced this type of feelings in healthy subjects. Delusional-like ideation was assessed with the schizotypal personality questionnaire. Thirty-four healthy subjects completed a semantic categorization task. Paranoid feelings were significantly enhanced by the induction. In these conditions, greater delusional-like ideation scores were associated with smaller N400 amplitudes and larger late positive components. Controlling for the two other schizotypal factors strengthened these results. These findings may help us understand why delusions persist.