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Biomedical subjects

S Weinstein

Publications and source records attributed to S Weinstein.

At least 19 recordsLinked to original sources
PubMed2006

Adverse effects to quality of life arising from treatment can recover with intermittent androgen suppression in men with prostate cancer.

Health-related quality of life (HQOL) research is a means of broadening the assessment of treatment effects. This longitudinal study investigated the dynamic change to quality of life (QOL) and testosterone dependant physiology in men commencing an intermittent maximal androgen blockade program (IMAB). Two hundred and fifty men were accrued to the multi-centre study of IMAB (Flutamide 250 mg TDS, Leuprolide 22.5 mg depot) ceasing treatment after 9 months if PSA <4 ng/ml, and restarting when PSA >20 ng/ml. QOL was assessed every 3 months for 30 months using the EORTC QLQ-C30 and EORTC QLQ-PR25 module. Data completion for the whole study was 90%. At baseline, our cohort was less symptomatic and had better function than the EORTC reference cohort, which may be related to a shift in clinical practice with time. Testosterone suppression (AS) lead to a significant reduction in global HQOL and deterioration in most function and symptom scales. During the off period, there was a trend of progressive improvement in HQOL that paralleled testosterone recovery but was slower than the rate of deterioration during the treatment phase. Maximum recovery of HQOL occurred most frequently by months 9-12. Testosterone recovery was slower and less complete in older men, and lead to concomitant poorer HOQL recovery. Whilst the magnitude of mean change to scale scores was small, there was a consistent and simultaneous deterioration during maximal androgen blockade (MAB) and improvement during androgen recovery. Older men are more likely to show an impaired testosterone recovery, and this was paralleled by a slower HQOL recovery. Newer methods of analysis to describe results in a way that has meaning to the individual patient are warranted.

Aged↗
PubMed2006

Hemorrhagic corpus luteum is associated with ovarian edema.

BACKGROUND: Most cases of ovarian edema are thought to result from intermittent ovarian/adnexal torsion. This study describes how, in some cases, this etiology was ruled out even though the edema was unexplained. STUDY OBJECTIVE: To evaluate the association between ovarian edema and hemorrhagic corpus luteum. SETTING: Department of gynecology in an urban medical center. PARTICIPANTS: Five patients admitted to the department of gynecology with a sonographic diagnosis of ovarian edema of unexplained etiology. RESULTS: Laparoscopy performed on three of five patients in whom a diagnosis of unexplained ovarian edema revealed hemorrhagic corpus luteum and ovarian edema. The remaining two patients displayed typical sonographic imaging of hemorrhagic corpus luteum and ovarian edema and they were managed expectantly. The affected ovaries were between 4.8 and 10 times larger than the unaffected ovaries. During follow-up, the affected ovaries returned to their normal size and appearance. CONCLUSIONS: Hemorrhagic corpus luteum can cause ovarian edema without interrupting the blood flow supply. The outcome of expectant management without any surgical intervention is the gradual disappearance of the ovarian edema in these patients and the return of ovaries to a normal sonographic appearance.

Adolescent↗
PubMed2004

fMRI language task panel improves determination of language dominance.

BACKGROUND: fMRI language tasks reliably identify language areas in presurgical epilepsy patients, but activation using single paradigms may disagree with the intracarotid amobarbital test (IAT). OBJECTIVE: To determine whether a panel of fMRI tasks targeting different aspects of language processing increases accuracy in determining hemisphere language dominance. METHODS: Twenty-six patients age 12 to 56 years, predominantly with temporal lobe epilepsy, were studied using whole-brain 1.5 T fMRI (echo planar imaging, blood oxygenation level-dependent) with three task categories using a block design: verbal fluency, reading comprehension, and auditory comprehension. fMRI t maps were visually rated at three thresholds. All patients had assessment of language lateralization by IAT. RESULTS: fMRI showed left dominance in 21 patients, right dominance in 2, and bilateral activation in 2; raters disagreed over a left vs right bilateral rating in 1 patient. There was full agreement between IAT and fMRI in 21 of 25 patients (IAT failed in 1). In three instances of partial disparity with IAT, the fMRI panel showed consistent findings across raters. Agreement between raters was excellent (partial disagreement in only one patient); the panel of tasks was superior to any single task for interrater agreement (Cramer V 0.93 [range 0.91 to 1.0] vs 0.72 [range 0.60 to 0.86]). CONCLUSIONS: A panel of fMRI language paradigms may be more accurate for evaluating partial epilepsy patients than a single task. A panel of tasks reduces the likelihood of nondiagnostic findings, improves interrater reliability, and helps confirm language laterality.

Adolescent↗
PubMed2002

Language dominance in partial epilepsy patients identified with an fMRI reading task.

BACKGROUND: fMRI language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment to quantitative region of interest (ROI) analysis. OBJECTIVE: To identify temporal language areas in patients with partial epilepsy using a reading paradigm with clinical and ROI interpretation. METHODS: Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared to a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AI) were calculated ([L-R]/[L+R]) and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had intracarotid amobarbital test (IAT). RESULTS: The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients, three had partial agreement, none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and 8 with ROI analysis. CONCLUSIONS: An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.

Adolescent↗
PubMed2002

Low incidence of abnormal (18)FDG-PET in children with new-onset partial epilepsy: a prospective study.

OBJECTIVE: Patients with refractory partial epilepsy often exhibit regional hypometabolism. It is unknown whether the metabolic abnormalities are present at seizure onset or develop over time. METHODS: The authors studied 40 children within 1 year of their third unprovoked partial seizure with EEG, MRI, and [(18)F]-fluorodeoxyglucose ((18)FDG)-PET (mean age at seizure onset = 5.8 years, range 0.9 to 11.9 years; mean epilepsy duration = 1.1 years, range 0.3 to 2.3 years; mean number of seizures = 30, range 3 to 200). The authors excluded children with abnormal structural MRI, except four with mesial temporal sclerosis and two with subtle hippocampal dysgenesis. (18)FDG-PET was analyzed with a region of interest template. An absolute asymmetry index, [AI], greater than 0.15 was considered abnormal. RESULTS: Thirty-three children had a presumptive temporal lobe focus, five frontotemporal, and two frontal. Mean AI for all regions was not different from 10 normal young adults, even when children less likely to have a temporal focus were excluded. Eight of 40 children (20%) had focal hypometabolism, all restricted to the temporal lobe, especially inferior mesial and inferior lateral regions. Abnormalities were ipsilateral to the presumed temporal lobe ictal focus. CONCLUSIONS: Abnormalities of glucose utilization may be less common and profound in children with new-onset partial seizures than in adults with chronic partial epilepsy. Although these patients' prognosis is uncertain, resolution of epilepsy after three documented seizures is uncommon. If the subjects develop a higher incidence of hypometabolism in the future with planned follow-up studies, metabolic dysfunction may be related to persistent epilepsy rather than present at seizure onset.

Brain↗
PubMed2001

The anticonvulsant effect of electrical fields.

The use of electrical fields to treat epilepsy is undergoing increased scrutiny as an alternative to medications and resective surgery. Much recent attention has been focused on ionic channels and seizure control; however, nonsynaptic mechanisms may be crucial for seizure onset, raising the possibility of using electrical field application to abort seizures. Furthermore, the inhibitory effects may outlast the immediate treatment and possibly be a prophylactic intervention. This paper reviews the use of brain stimulation for treatment of epilepsy, but also cites instances where the antithetical results occur. The greatest detail focuses on disrupting the onset or shortening the seizure. The paper does not extensively review deep brain or vagal nerve stimulation.

Animals↗
PubMed2001

Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in patients with asthma.

BACKGROUND: Environmental imperatives to eliminate the use of chlorofluorocarbon (CFC) propellants in metered-dose inhalers have led to the development of metered-dose inhalers with the hydrofluoroalkane (HFA-134a) propellants. OBJECTIVES: To evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and to compare the efficacy and safety of Ventolin CFC, Ventolin HFA, and placebo in patients with asthma. METHODS: Multicenter, double-blind, randomized safety and efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus placebo for 12 weeks in 313 patients with asthma aged 12 years and older who received Ventolin CFC during a 3-week run-in period. RESULTS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and other measures of asthma control at levels comparable with run-in baseline. Serial pulmonary function testing demonstrated that both Ventolin treatments had significantly greater mean improvement in FEV1 over baseline than the placebo group at treatment day 1 and weeks 6 and 12 (P < .001). Both Ventolin groups had comparable pulmonary function at every visit. Predose FEV1 values were maintained or improved over time with all treatments. Treatments were well-tolerated. The adverse event profile for both Ventolin treatments was comparable with placebo. No clinically relevant effects on ECG, vital signs, or clinical laboratory tests were noted. Asthma exacerbation rates were 4% to 5% in the Ventolin groups and slightly higher (8%) in the placebo group. CONCLUSIONS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained comparable asthma control with a similar safety profile.

Adolescent↗
PubMed2000

Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome.

The clinical presentation of mitochondrial DNA (mtDNA) disorders is quite diverse. Very often, the initial symptoms do not fit a specific disease, and diagnosis is difficult to make. We describe a patient who presented with macrocytic anemia. Extensive biochemical and clinical work-up failed to provide an etiology for the macrocytic anemia. The patient over the course of 6 years developed gait problems, exercise intolerance, episodic vomiting, short stature, dermatological problems, and recurrent infection. At age 8 years she had encephalopathy with ataxia and dysphagia. The presence of elevated lactate, bilateral basal ganglia calcification, and ragged red fibers led to mtDNA mutational analysis. A novel 4.4-kb deletion from nucleotide position 10,560 to nucleotide position 14, 980 was identified in muscle biopsy. The same heteroplasmic mtDNA deletion was present in blood, buccal cells, and hair follicles, but not in mother's blood, consistent with sporadic mutation in the patient. This case emphasizes the importance of considering mtDNA disorder in patients with multisystemic symptoms that cannot be explained by a specific diagnosis.

Anemia, Macrocytic↗
PubMed2000

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Adolescent↗
PubMed2000

Dissociation of immunologic and virologic responses to highly active antiretroviral therapy.

OBJECTIVE: Immunologic markers, levels of HIV DNA, and infectious HIV were compared in partial responders (PR) to HAART who had high plasma HIV RNA levels but stable or increasing levels of CD4+ peripheral blood mononuclear cells (PBMC), and patients with complete failure (CF) who had very low or decreasing levels of CD4+ PBMC and high plasma HIV RNA levels. DESIGN AND METHODS: CD4 and CD8 levels were monitored by flow cytometry. Beta2-microglobulin (beta2M) and neopterin levels were measured by quantitative enzyme immunoassays. Plasma and PBMC from 11 PR and 13 CF were analyzed for infectious HIV levels in limiting dilution cultures. Polymerase chain reaction (PCR) assays were used to quantify cellular HIV DNA and plasma HIV RNA. RESULTS: In comparison with CF, PR had little or no CD4+ cell loss, a substantial increase in CD8+ cells, significantly fewer positive plasma HIV cultures (p = .03), lower frequencies of infectious HIV in total PBMC (p = .005) and in CD4+ PBMC (p < .001), and lower frequencies of HIV DNA in CD4+ PBMC (p = .007). CONCLUSIONS: Lower levels of infectious HIV and a lower frequency of CD4+ PBMC that contain "productive" HIV DNA in PR as compared with CF may contribute to the stable or increasing CD4+ PBMC levels of the PR. However, HAART may also have effects on lymphocyte homeostasis independent of its antiviral activity.

Anti-HIV Agents↗
PubMed2000

Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

Administration, Oral↗
PubMed2000

Genetic and biochemical manipulations of the small ribosomal subunit from Thermus thermophilus HB8.

Crystals of the small ribosomal subunit from Thermus thermophilus diffract to 3A and exhibit reasonable isomorphism and moderate resistance to irradiation. A 5A MIR map of this particle shows a similar shape to the part assigned to this particle within the cryo-EM reconstructions of the whole ribosome and contains regions interpretable either as RNA chains or as protein motifs. To assist phasing at higher resolution we introduced recombinant methods aimed at extensive selenation for MAD phasing. We are focusing on several ribosomal proteins that can be quantitatively detached by chemical means. These proteins can be modified and subsequently reconstituted into depleted ribosomal cores. They also can be used for binding heavy atoms, by incorporating chemically reactive binding sites, such as -SH groups, into them. In parallel we are co-crystallizing the ribosomal particles with tailor made ligands, such as antibiotics or cDNA to which heavy-atoms have been attached or diffuse the latter compounds into already formed crystals.

Bacterial Proteins↗
PubMed2000

Variant chromophobe renal cell carcinoma.

Separation of renal cell tumors into different prognostic groups is an imperative function of the diagnostic pathologist. Recently, chromophobe renal carcinoma has been described as a tumor that is morphologically distinct from conventional "clear cell" carcinoma and that has a low metastatic potential. Identification is based on routine light microscopic features and is confirmed by special stains, immunohistochemistry, and electron microscopy. We present a variant of chromophobe renal carcinoma that did not show the typical cytomorphologic features on light microscopy after formaldehyde fixation. After fixation in Solufix (a commercial fixative), these features were recognized and the diagnosis was confirmed. The tumor also showed an unusual form of calcification and psammoma body formation not previously recognized in chromophobe tumors. Molecular biological assessment was inconclusive, but excluded a chromosome 3p deletion usually found in conventional renal carcinoma. The use of a different primary fixative may provide a cost-effective screening tool to detect variant renal tumors and may have important prognostic implications.

Aged↗
PubMed2000

Targeting exposed RNA regions in crystals of the small ribosomal subunits at medium resolution.

Within the framework of ribosomal crystallography, the small subunits are being analyzed, using crystals diffracting to 3 A resolution. The medium resolution electron density map of this subunit, obtained by multiple isomorphous replacement, show recognizable morphologies, strikingly similar to the functional active conformer of the small ribosomal subunit. It contains elongated dense features, traceable as RNA chains as well as globular regions into which the structures determined for isolated ribosomal proteins, or other known structural motifs were fitted. To facilitate unbiased map interpretation, metal clusters are being covalently attached either to the surface of the subunits or to DNA oligomers complementary to exposed ribosomal RNA. Two surface cysteines and the 3' end of the 16S ribosomal RNA have been localized. Targeting several additional RNA regions shed light on their relative exposure and confirmed previous studies concerning their functional relevance.

Crystallography, X-Ray↗