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Biomedical subjects

J Levine

Publications and source records attributed to J Levine.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease.

BACKGROUND: Pompe disease is a progressive metabolic neuromuscular disorder resulting from deficiency of lysosomal acid alpha-glucosidase (GAA). Infantile-onset Pompe disease is characterized by cardiomyopathy, respiratory and skeletal muscle weakness, and early death. The safety and efficacy of recombinant human (rh) GAA were evaluated in 18 patients with rapidly progressing infantile-onset Pompe disease. METHODS: Patients were diagnosed at 6 months of age and younger and exhibited severe GAA deficiency and cardiomyopathy. Patients received IV infusions of rhGAA at 20 mg/kg (n = 9) or 40 mg/kg (n = 9) every other week. Analyses were performed 52 weeks after the last patient was randomized to treatment. RESULTS: All patients (100%) survived to 18 months of age. A Cox proportional hazards analysis demonstrated that treatment reduced the risk of death by 99%, reduced the risk of death or invasive ventilation by 92%, and reduced the risk of death or any type of ventilation by 88%, as compared to an untreated historical control group. There was no clear advantage of the 40-mg/kg dose with regard to efficacy. Eleven of the 18 patients experienced 164 infusion-associated reactions; all were mild or moderate in intensity. CONCLUSIONS: Recombinant human acid alpha-glucosidase is safe and effective for treatment of infantile-onset Pompe disease. Eleven patients experienced adverse events related to treatment, but none discontinued. The young age at which these patients initiated therapy may have contributed to their improved response compared to previous trials with recombinant human acid alpha-glucosidase in which patients were older.

Dose-Response Relationship, Drug↗
PubMed2005

CSF homocysteine is not elevated in schizophrenia.

Homocysteine is a neurotoxic amino acid originally found to be an independent risk factor for cardiovascular and cerebral vascular disease and more recently suggested to be a risk factor for Alzheimer's disease. Several authors have observed high plasma homocysteine levels among schizophrenia patients. We reported that such high levels characterize young male schizophrenia patients. We now studied two groups of schizophrenia patients (N=41) and controls (N=29) for CSF homocysteine levels. No difference was found for CSF homocysteine levels between schizophrenia patients and controls (p=.041 for Study A and p=.52 for Study B).

Adolescent↗
PubMed2005

Nutritional and life style determinants of plasma homocysteine in schizophrenia patients.

Recently, homocysteine levels have been reported to be elevated in young male schizophrenic patients. Since smoking, obesity, low folate or low vitamin B12 and various medications can increase homocysteine levels, we studied these variables and other clinical variables in 258 schizophrenic patients. A multiple linear regression for plasma homocysteine was performed on variables that were significantly related to plasma homocysteine. Variables predicting homocysteine levels in schizophrenic patients include gender, plasma folate levels, plasma vitamin B12 levels, mean red blood cell corpuscular volume and diastolic blood pressure. Only 24% of the variance in male patients was explained by the model. The reason for elevated plasma homocysteine in some schizophrenic populations remains unclear.

Adolescent↗
PubMed2005

The use of laparoscopic liver biopsies in pediatric patients with hepatic dysfunction following allogeneic hematopoietic stem cell transplantation.

Hepatic dysfunction following hematopoietic stem cell transplantation (HSCT) is common, but making the correct diagnosis can be challenging. Liver biopsies can serve as an important diagnostic tool when the etiology cannot be clearly determined by laboratory data, physical examination, and imaging studies. We reviewed 12 consecutive pediatric patients (seven males, five females, age 9-23 years) who received allogeneic HSCT and underwent a laparoscopic-guided liver biopsy for hepatic dysfunction of unknown etiology from 1998 to 2005. Biopsies were performed using a single-port technique with a 16 or 18 gauge, spring-loaded biopsy gun. The time from HSCT to biopsy ranged from 31 days to 821 days (median 92 days). No intra- or postoperative complications were observed. The initial clinical diagnosis was confirmed in seven patients, whereas the initial working diagnosis was inaccurate in the remaining five patients. Our results suggest that laparoscopic-guided liver biopsy is an informative and safe procedure in pediatric HSCT recipients; this approach helped delineate the true cause of hepatic dysfunction and changed our therapeutic approach in approximately 40% of the patients reviewed. While the safety record at our institution appears promising, a larger multi-institutional study would be necessary to more accurately describe the overall efficacy of this procedure in pediatric HSCT patients.

Adolescent↗
PubMed2004

GSK-3beta in cerebrospinal fluid of schizophrenia patients.

Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970's with few definitive results. We have recently found 40% reduced protein levels of GSK-3beta in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3beta was not successful. In this study we aimed to find whether the reduction in brain GSK-3beta is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3beta protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients' postmortem brain.

Adult↗
PubMed2003

Effects of acetyl-L-carnitine and myo-inositol on high-energy phosphate and membrane phospholipid metabolism in zebra fish: a 31P-NMR-spectroscopy study.

Acetyl-L-carnitine (ALCAR) and myo-inositol are reported to enhance motor activity in animal models; modulate membrane phospholipid metabolism (ALCAR and myo-inositol) and high-energy phosphate metabolism (ALCAR) back to normal; and be effective treatments of major depression in humans. Fish in general and zebra fish in particular present unique animal models for the in vivo study of high-energy phosphate and membrane phospholipid metabolism by noninvasive in vivo 31P NMR. This 31P NMR study of free-swimming zebra fish showed that both ALCAR and myo-inositol decreased levels of phosphodiesters and inorganic orthophosphate and increased levels of PCr in the fish. These findings demonstrate both ALCAR and myo-inositol modulate membrane phospholipid and high-energy phosphate metabolism in free-swimming zebra fish.

Acetylcarnitine↗
PubMed2003

Tracmor system for measuring walking energy expenditure.

OBJECTIVE: Walking is an important mode of exercise and is likely to represent a major component of nonexercise activity thermogenesis. The question arises, how best to quantify walking-energy expenditure (EE) in free-living individuals. The triaxial accelerometer for movement registration (Tracmor) is a valid measure of body displacement and so we wanted to evaluate this tool for quantifying walking-EE. HYPOTHESIS: In this study, we test the hypothesis that walking-EE, measured in a Room Calorimeter, can be predicted from Tracmor output using a regression equation derived from a brief Tracmor/treadmill/Metabolic Cart protocol. DESIGN: First, 11 healthy subjects completed a 40-min procedure whereby they wore a Tracmor unit and walked on a treadmill at 0, 1, 2 and 3 mph while EE was measured using a Metabolic Cart. This allowed a regression equation to be defined for each subject to convert Tracmor output to EE. Each subject then entered a Room Calorimeter wearing the Tracmor Unit and walked at two self-selected velocities ('slow', 'fast') while EE was measured. 'Tracmor/regression equation' predictions of walking-EE were compared with Room Calorimeter measurements of walking-EE for the two velocities. RESULTS: The 'Tracmor/regression equation' prediction of EE for walking slowly was 6.36+/-1.67 kJ/min, and for walking fast it was 11.0+/-2.60 kJ/min. Room Calorimeter measurements were 6.43+/-1.85 and 10.9+/-3.03 kJ/min, respectively. The intraclass correlation coefficient for slow-paced walking was 0.93 (P<0.001), and for fast-paced walking it was 0.82 (P<0.005). CONCLUSIONS: When combined with laboratory measures of EE, the Tracmor accelerometer provides useful data on walking-EE and is applicable to free-living individuals.

Acceleration↗
PubMed2003

A phase I-II study of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) for B cell non-Hodgkin's lymphoma prior to and after high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT).

This phase I-II study describes the safety of rituximab, ifosfamide, mitoxantrone and etoposide (R-IME) as an induction regimen prior to high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT), and rituximab given post-HDC-ASCT for B cell non-Hodgkins's lymphoma. This study also measured the effect on disease burden and stem cell contamination. Patients with relapsed, refractory or poor risk B cell lymphomas were eligible. Patients were treated with two cycles of R-IME; all non-progressing patients under-went a third cycle and peripheral blood stem cell (PBSC) collection. Patients underwent HDC-ASCT and those patients in remission after HDC-ASCT were treated with four additional doses of rituximab. Tumor cell contamination was measured at baseline and in the PBSC. Serial immunoglobulin levels were measured. Patients were followed for time to treatment failure (TTF) and overall survival (OS). Thirty-two patients were enrolled. Thirty patients had at least stable disease after two cycles of R-IME. Twenty-nine underwent stem cell collection. The response rate to R-IME induction was 77% (20/26) with 35% (9/26) complete response(CR). Stem cell mobilization was successful in 93% (27/29) of patients. The response rate to R-IME induction and HDC-ASCT was 95% with a confirmed CR of 68%. Median follow-up was 28 months; the median TTFand OS have not been reached. There was a significant decline in stem cell tumor cell contamination and a significant decline in IgG without an increase in infections. Forty-three per cent of patients had transient neutropenia after post-transplant rituximab. R-IME is an effective cytoreductive and mobilization regimen. There appears to be a reduction in the number of lymphoma cells in the stem cell product and the toxicity is manageable.

Adult↗
PubMed2002

Clozapine: its impact on aggressive behavior among patients in a state psychiatric hospital.

Clozapine has shown consistent efficacy against positive symptoms of psychoses, and emerging reports indicate improvements in aggression and suicidality. This study evaluated the impact of clozapine aggression in a psychiatric hospital. Over a three year period, 137 subjects with schizophrenia or schizoaffective disorder received clozapine, of whom nearly 50% (n=69) experienced seclusion or restraint. Using a mirror-image study design, seclusion and restraint rates were computed per patient-month pre-clozapine and compared during clozapine treatment to a maximum of 12 months in either direction. The rest of the hospital not receiving clozapine served as a comparator group. Statistically significant reductions occurred in both seclusion (0.44+/-0.46 vs. 0.16+/-0.32, z=-3.91, p=0.0003) and restraint (0.34+/-0.47 vs. 0.08+/-0.23, z=-2.27, p=0.032) during clozapine treatment as compared with the pre-clozapine period. The comparator group experienced a low rate of seclusion and restraint throughout. While there are limitations to a mirror-image design, this study supports the emerging data on the benefits of clozapine for aggressive and violent patients with psychoses. Preliminary data suggests other second generation antipsychotic agents may have similar effects.

Adult↗
PubMed2001

Chronic myo-inositol increases rat brain phosphatidylethanolamine plasmalogen.

BACKGROUND: Oral myo-inositol (12--18 g/day) has shown beneficial effect in placebo-controlled studies of major depression, panic disorder, and obsessive compulsive disorder, and preliminary data suggest it also may be effective in bipolar depression. Evidence linking antidepressant activity to membrane phospholipid alterations suggested the examination of acute and chronic myo-inositol effects on rat brain membrane phospholipid metabolism. METHODS: With both (31)P nuclear magnetic resonance (NMR) and quantitative high-performance thin-layer chromatography (HPTLC; hydrolysis) methods, rat brain phospholipid levels were measured after acute (n = 20, each group) and chronic myo-inositol administration (n = 10, each group). With (31)P NMR, we measured myo-inositol rat brain levels after acute and chronic myo-inositol administration. RESULTS: Brain myo-inositol increased by 17% after acute myo-inositol administration and by 5% after chronic administration, as compared with the control groups. Chronic myo-inositol administration increased brain phosphatidylethanolamine (PtdEtn) plasmalogen by 10% and decreased brain PtdEtn by 5%, thus increasing the ratio PtdEtn plasmalogen (PtdEtn-Plas)/PtdEtn by 15%. Phosphatidylethanolamine plasmalogen levels quantified by (31)P NMR and HPTLC were highly correlated. The validity and reliability of the (31)P NMR method for phospholipid analysis were demonstrated with phospholipid standards. CONCLUSIONS: The observed alteration in the PtdEtn-Plas/PtdEtn ratio could provide insights into the therapeutic effect of myo-inositol in affective disorders.

Animals↗
PubMed2001

Anxiety disorders and major depression, together or apart.

This paper will discuss the relationship between anxiety and depression. We will begin with a brief historical perspective. We will then move into the twentieth century, with a focus on the 1950s, at which time the introduction of pharmacological treatment options revolutionized the field of psychiatry. The use of psychiatric medications and the observation of treatment response provided an additional means of understanding the relationship between anxiety and depression. From the late 1970s to the 1990s, it became apparent that various medications possessed wider therapeutic profiles than were previously recognized. For example, many medications were found to be efficacious in both anxiety and depressive disorders. These expanded therapeutic profiles provided additional clues to fuel our thinking about the relationship between anxiety and depression. The two major objectives of this paper are, first, to describe and formalize a process of pharmacological dissection and, second, to consider how this process might contribute to our search for a better understanding of the relationship between anxiety and depression.

Anti-Anxiety Agents↗
PubMed2001

Differentiating primary pathophysiologic from secondary adaptational processes.

The following manuscript is mainly conceptual in nature. It should be read with reservation since the relevance of its suggestions have yet to be proven. Basically it proposes two rules for the differentiation between primary illness-related pathophysiological vs. secondary adaptational processes. These rules may guide hypotheses generation for further research that is aimed at understanding psychiatric disorders and their shared and unshared mechanisms. For example, in the case of anxiety disorders and depression, it may be of interest to learn if their shared properties are of primary pathophysiological or secondary adaptational significance. We first present some historical observations on the development of the concept of "secondary adaptational processes." We assume such adaptational processes are generated by the organism in order to compensate for primary pathophysiological malfunction or impairment. Next, we propose rules that may enable the dissection of secondary adaptational from primary pathophysiological processes. We also discuss the possible implications of designing studies to sort out these processes, suggesting that the understanding of adaptational processes, may explain the effects of "placebo treatment." Finally we illustrate the application of these rules by two examples: a) amygdala activation, a biological alteration shared by anxiety disorders and major depression and b) elevated plasma soluble interleukin 2 receptor, an unshared property by anxiety disorders and major depression. Also, the first example relates to a biological perturbation associated with a primary pathophysiological mechanism, while the second represents a biological alteration associated with secondary adaptational processes.

Adaptation, Psychological↗
PubMed2001

Effect of inositol on bulimia nervosa and binge eating.

OBJECTIVES: This study aimed to determine whether inositol has therapeutic value in patients with bulimia nervosa and binge eating. METHOD: A double-blind crossover trial using 18 g inositol versus placebo was performed in 12 patients for 6 weeks in each arm. RESULTS: Inositol was significantly better than placebo on the Global Clinical Impression, the Visual Analogue Scale, and the Eating Disorders Inventory. DISCUSSION: Inositol is as therapeutic in patients with bulimia nervosa and binge eating as it is in patients with depression and panic and obsessive-compulsive disorders. This increases its parallelism with serotonin selective reuptake inhibitors.

Adult↗
PubMed2001

Comparison of open and endoscopic treatment of posttraumatic posterior urethral strictures.

The purpose of this study was to compare the invasiveness, morbidity, and outcomes of open versus endoscopic treatment of posttraumatic posterior urethral strictures. We compared two groups of men with strictures of the posterior urethra after pelvic fracture: Group I (n = 6) underwent cut-to-the-light procedures before 1995, and group II (n = 9) underwent perineal anastomotic urethroplasty after 1995. The operating time and blood loss were lower in the endoscopic group, but no other significant differences in morbidity or invasiveness were found. All six patients in group I required multiple secondary procedures: Three reached a stable voiding pattern after a mean of three interventions, two required subsequent urethroplasty, and one was lost to long-term follow-up. Normal voiding was achieved in all group II patients, although two (22%) required single internal urethrotomy within 3 months after surgery. The data show the comparable morbidity of open urethroplasty and cut-to-the-light procedures and support an aggressive surgical approach for the delayed treatment of posttraumatic posterior urethral strictures. Other than a reduced operating time, endoscopic procedures offered no compelling advantage over surgical reconstruction.

Adolescent↗
PubMed2001

The response of adult oligodendrocyte progenitors to demyelination in EAE.

Cells with the phenotypic characteristics of oligodendrocyte progenitors (NG2+/PDGF alpha R+/O4+) are found throughout the adult mammalian CNS in numbers similar to microglia. They are a reactive glial cell population and respond to demyelination by increasing in number, thereby repopulating the lesion site with cells capable of differentiating into remyelinating oligodendrocytes. Direct evidence that they differentiate into remyelinating cells is missing, although this is the most likely scenario. Cells with the same phenotype are found in normal human CNS tissue and also in chronic MS lesions. Further studies on this intriguing cell type are necessary in order to understand the molecular signals involved in their reaction to injury, particularly in multiple sclerosis.

Animals↗
PubMed2001

Long-term effects of topiramate on bipolar mood instability, weight change and glycemic control: a case-series.

Topiramate is an antiepileptic agent, which is being investigated as a mood-stabilizer. Three obese individuals with DSM-IV bipolar I disorder and type II diabetes mellitus received topiramate treatment in combination with antipsychotics and valproate or carbamazepine. In addition to improved mood stability, these individuals lost between 16 to 20.5% of their pre-topiramate body weight and also achieved significant glycemic control.

Adult↗