Search PubMed⌕ Search

Biomedical subjects

D M Lefkowitz

Publications and source records attributed to D M Lefkowitz.

15 recordsLinked to original sources

Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators.

We examined the effect of the neuroprotective and neuroreparative agent citicoline on the growth of cerebral ischemic lesions in a double-blind placebo-controlled study involving patients with acute ischemic stroke using diffusion-weighted magnetic resonance imaging (DWI). Patients with acute ischemic stroke symptom onset 24 hours or less before the start of treatment, National Institutes of Health Stroke Scale (NIHSS) scores of 5 or higher, and lesions of 1 to 120 cc in cerebral gray matter by DWI were enrolled. DWI, T2-weighted magnetic resonance imaging (MRI), perfusion-weighted MRI, and magnetic resonance angiography were obtained at baseline, week 1, and week 12. Citicoline (500 mg/day) was administered orally for 6 weeks, and patients were followed for 12 weeks. The primary assessment was progression of ischemic lesion volume from baseline to 12 weeks as measured by MRI. A total of 100 patients entered the study. The primary MRI analysis included 40 placebo-treated patients and 41 citicoline-treated patients with both baseline and week 12 MRI data and failed to demonstrate a significant difference in lesion volume change from baseline to week 12. From baseline to week 12, ischemic lesion volume [all values mean (SE)] expanded by 180% (107) among placebo-treated patients compared with 34% (19) among citicoline-treated patients. In a secondary analysis, lesion volume decreased from week 1 to week 12 by 6.9 cc (2.8) on placebo versus 17.2 cc (2.6) on citicoline. Baseline variables that were predictors of change in lesion size over 12 weeks were the volume of hypoperfusion (strongest association), baseline NIHSS score, lesion volume on DWI, arterial lesion by magnetic resonance angiography, and categorized elapsed time (< or =12 or >12 hours) from stroke onset to first dose. A marked association between lesion volume reduction and improvement of NIHSS score by seven or more points was observed. Significant correlations between lesion volumes and clinical measures were found, replicating values reported in the literature for smaller case series. We observed a reduction in lesion volume growth from baseline to week 12 with citicoline treatment, with a significantly greater reduction in volume from week 1 to week 12 with citicoline. We found a significant inverse relationship between lesion volume change over 12 weeks as measured by MRI and clinical outcome for ischemic stroke. This relationship supports the role of DWI as a surrogate marker of clinically meaningful lesion progression in stroke clinical trials. The hypothesis that citicoline reduces lesion growth and improves clinical outcome will be tested further.

Aged↗

Clinical studies of families with hearing loss attributable to mutations in the connexin 26 gene (GJB2/DFNB1)

OBJECTIVE: This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of childhood deafness is estimated at 1/500. Half of this hearing loss is genetic and approximately 80% of genetic hearing loss is nonsyndromic and inherited in an autosomal recessive manner. Approximately 50% of childhood nonsyndromic recessive hearing loss is caused by mutations in the connexin 26 (Cx26) gene (GJB2/DFNB1), making it the most common form of autosomal recessive nonsyndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for approximately 75% to 80% of mutations at this gene. METHODS: Hearing loss was examined in 46 individuals from 24 families who were either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic emissions, auditory brainstem response, temporal bone computed tomography, electrocardiography, urinalyses, dysmorphology, and thyroid function. RESULTS: Although all persons had hearing impairment, no consistent audiologic phenotype was observed. Hearing loss varied from mild-moderate to profound, even within the group of families homozygous for the common mutation 35delG, suggesting that other factors modify the phenotypic effects of mutations in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid dysfunction, heart conduction defect, urinalyses, dysmorphic features, or retinal abnormality were noted. CONCLUSION: Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).

Child↗

Posttraumatic innominate artery aneurysm with occlusion of the common carotid artery at its origin by an intimal flap.

Blunt trauma involving the innominate and carotid arteries is a rare occurrence that can be lethal or have serious neurologic sequelae. To our knowledge this is the first reported case in the international literature describing the association of posttraumatic innominate artery aneurysm with total occlusion and thrombosis of the common carotid artery at its origin by an intimal flap. The diagnostic problems created by this unusual injury are discussed. In this case the patency of the distal portion of the common and internal carotid arteries was demonstrated by magnetic resonance angiography (MRA), whereas color duplex and digital arteriographic studies were unsuccessful. This demonstration was crucial to patient management. Since no studies are available comparing color duplex imaging, conventional arteriography, and MRA in the evaluation of blunt carotid trauma, this case study is presented to demonstrate the utility of MRA in emergency situations. In addition, we analyze the possible pathogenesis and discuss the surgical treatment.

Adolescent↗

Adjusted resistive index: a method to estimate rapidly renal blood flow: preliminary validation in hypertensives.

The Doppler RI, measured in a blinded fashion, was correlated with RBF, RVR, and GFR calculated by simultaneous clearance measurements. Nine hypertensive patients were studied weekly while receiving increasing doses of the vasodilator minoxidil. In 36 studies, RI was significantly correlated with RBF (r = -0.42) but not with RVR or GFR. When RI values were adjusted for ERV, correlations strikingly improved and were further improved by adjustment for pulse pressure. The ARI allowed semiquantitative predictions of RBF and RVR more accurately than blood urea nitrogen or serum creatinine levels. Correlation with GFR was weak.

Adult↗

Treatment options in high-grade brain tumors: brain brachytherapy.

The extremely poor prognosis of high-grade brain tumors (glioblastoma multiforme and anaplastic astrocytomas) has been well documented in the literature. Almost 90% of patients die within 18 months after therapy, most commonly because of local persistence of the tumor, which may be controlled if a sufficient amount of irradiation can be delivered. Currently, postoperative radiation therapy offers the best median survival rate. However, the response to external-beam radiation therapy has reached a plateau because of the intolerance of healthy brain tissue to excessive irradiation. To treat these tumors, brachytherapy (interstitial implantation of radioactive sources) can be used with debulking surgery. This therapy is becoming an effective alternative to conventional external-beam radiation therapy, since it allows a higher dose to be delivered to the tumor bed without damaging the surrounding healthy brain tissue. With continual refinements of the technique, brachytherapy, performed by a skilled brachytherapy team, offers an opportunity to improve patient survival.

Astrocytoma↗

PET of infant in persistent vegetative state.

This is the first report of cranial positron emission tomography findings of an infant in a persistent vegetative state. Serial positron emission tomography/2-deoxy-2[18F]fluoro-D-glucose studies demonstrated persistent global reduction of cerebral glucose metabolism, results similar to those found in adults in persistent vegetative states. Positron emission tomography may be useful in confirming this clinical diagnosis in infants.

Blood Glucose↗