Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).     

Use of a food frequency questionnaire in American Indian and Caucasian pregnant women: a validation study

Background  

Food frequency questionnaires (FFQs) have been validated in pregnant women, but few studies have focused specifically on low-income women and minorities. The purpose of this study was to examine the validity of the Harvard Service FFQ (HSFFQ) among low-income American Indian and Caucasian pregnant women.     

Short-term moderate hypocapnia augments detection of optimal cerebral perfusion pressure

An autoregulation-oriented strategy has been proposed to guide neurocritical therapy toward the optimal cerebral perfusion pressure (CPPOPT). The influence of ventilation changes is, however, unclear. We sought to find out whether short-term moderate hypocapnia (HC) shifts the CPPOPT or affects its detection. Thirty patients with traumatic brain injury (TBI), who required sedation and mechanical ventilation, were studied during 20?min of normocapnia (5.1±0.4?kPa) and 30 min of moderate HC (4.4±3.0?kPa). Monitoring included bilateral transcranial Doppler of the middle cerebral arteries (MCA), invasive arterial blood pressure (ABP), and intracranial pressure (ICP). Mx -autoregulatory index provided a measure for the CPP responsiveness of MCA flow velocity. CPPOPT was assessed as the CPP at which autoregulation (Mx) was working with the maximal efficiency. During normocapnia, CPPOPT (left: 80.65±6.18; right: 79.11±5.84?mm Hg) was detectable in 12 of 30 patients. Moderate HC did not shift this CPPOPT but enabled its detection in another 17 patients (CPPOPT left: 83.94±14.82; right: 85.28±14.73?mm Hg). The detection of CPPOPT was achieved via significantly improved Mx-autoregulatory index and an increase of CPP mean. It appeared that short-term moderate HC augmented the detection of an optimum CPP, and may therefore usefully support CPP-guided therapy in patients with TBI.     

Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA

BACKGROUND: Suboptimal CD4+ T cell recovery during antiretroviral therapy (ART) is a common clinical dilemma. METHODS: We analyzed viral and immunologic predictors of CD4+ T cell recovery in 116 human immunodeficiency virus type 1 (HIV-1)-infected subjects who had suppressed viremia (< or = 50 copies/mL) while receiving ART. Successive measurements of T cell immunophenotypes and cellular HIV-1 DNA levels were obtained before and during receipt of ART. On the basis of increases in the CD4+ T cell count, subjects were classified as immunologically concordant (demonstrating an increase of > or = 100 CD4+ T cells/mm3) or discordant (demonstrating an increase of <100 CD4+ T cells/mm3) after 48 weeks of ART. RESULTS: In adjusted analyses, CD4+ and CD8+ T cell activation at baseline was negatively associated with immunologic concordance at week 48 of ART (odds ratio [OR], 0.80 [P = .04] and 0.67 [P = .02], respectively). High memory (CDRA(-)CD62L-) CD8+ T cell counts at baseline (OR, 0.33 [P = .05]) predicted less CD4+ T cell recovery, whereas increased naive CD4+ T cell counts were associated with higher increases in CD4+ T cells (OR, 1.19 [P = .052]). Neither the cell-associated HIV-1 DNA level at baseline (P = .32) nor the cell-associated HIV-1 DNA level at week 48 of ART (P = .42) was associated with immunologic concordance during ART. CONCLUSIONS: These results support the potential clinical usefulness of the baseline determination of immune activation and maturation subsets in the prediction of CD4+ T cell recovery during viral suppression. Furthermore, identification of individuals with reduced potential for CD4+ T cell recovery during ART may provide a rationale for the initiation of early therapy for some patients.     

The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

Rationale

Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.

Objectives

The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).

Methods

The inhibitor was administered intracerebroventricularly in liposomes.

Results

L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.

Conclusions

It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor’s effect with intracerebroventricular inositol would be an important further step in proof.