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Biomedical subjects

J Levine

Publications and source records attributed to J Levine.

At least 19 recordsLinked to original sources
PubMed1999

Nickel-catalyzed N-terminal oxidative deamination in peptides containing histidine at position 2 coupled with sulfite oxidation.

Peptides containing histidine at position 2 were observed to undergo spontaneous N-terminal oxidative deamination in aqueous solution in the presence of Ni(II), sulfite, and ambient oxygen. The reaction resulted in the formation of a free carbonyl on the N-terminal alpha-carbon (alpha-ketoamide) and was catalytic with respect to nickel. This oxidative deamination was confirmed by 13C NMR, 1H NMR, mass spectrometry, and chemical tests. No evidence of modification of histidine was found. It was demonstrated that the nickel-dependent N-terminal oxidative deamination also occurred in His-2 peptides using potassium peroxymonosulfate (oxone) as an oxidant. When oxone was used, oxygen was not required for the deamination to proceed. The results suggest that both nickel-catalyzed reactions (sulfite and oxygen, and oxone) produce an imine intermediate that spontaneously hydrolyzes to form the free carbonyl. These findings may provide a physiologically relevant model for oxidative carbonyl formation in vivo, as well as a useful method for producing a site-specific carbonyl on peptides and proteins.

Chromatography, High Pressure Liquid↗
PubMed1999

Combination of inositol and serotonin reuptake inhibitors in the treatment of depression.

BACKGROUND: Inositol has been reported to be an effective treatment in depression, and we hypothesized that inositol addition might enhance or speed up response to serotonin selective reuptake inhibitors (SSRI). METHODS: Twenty-seven depressed patients completed a double-blind controlled 4-week trial of SSRI plus placebo or SSRI plus inositol. Hamilton Depression Rating Scale was used as an assessment tool at baseline, and 1, 2, 3, and 4 weeks. RESULTS: No significant difference was found between the two treatment groups. CONCLUSIONS: Previous studies combining different effective antidepressant therapies similarly found no evidence for additive effects [e.g., monoamine oxidase inhibitors (MAOI) plus tricyclic antidepressants (TCA), TCA plus lithium]. By contrast, augmentation by lithium or MAOI after a failed course of antidepressant treatment is effective and should be studied with inositol.

Adult↗
PubMed1999

Frequency of digital rectal examination in children with chronic constipation.

OBJECTIVES: To determine the frequency of performance of digital rectal examination by primary care practitioners on children with chronic constipation and to assess its effect on therapy. PATIENTS AND METHODS: One hundred twenty-eight children referred for chronic constipation to the Division of Pediatric Gastroenterology at Schneider Children's Hospital, New Hyde Park, NY, as well as their parents were questioned as to whether a digital rectal examination was ever performed prior to referral. All children underwent subsequent digital rectal examination by a pediatric gastroenterologist and recommended treatment regimens were compared with pretreatment regimens. The patients evaluated were a mix of private-insurance and Medicaid patients referred by pediatricians in the general community. RESULTS: Ninety-eight (77%) of the children referred for chronic constipation were found to have never had a digital rectal examination performed prior to referral. Fifty-three (54%) of these children were found to have fecal impaction. Only 19 (21%) were found to have minimal to no stool retention on digital examination. Enema therapy had been infrequently used to "clean out" the colon in referred children. Seventy percent were treated with multiple enema therapy following digital rectal examination. Organic causes of constipation were identified in 3 patients. CONCLUSIONS: Digital rectal examination is often not performed in the examination of the child with chronic constipation. The digital examination can help differentiate functional constipation from an organic process and may alter the course of therapy.

Adolescent↗
PubMed1999

Acute flank pain: a modern approach to diagnosis and management.

Acute flank pain is a common and complex clinical problem. In addition to flank pain caused by ureterolithiasis, other urinary and extraurinary abnormalities can result in a similar clinical picture. Unenhanced CT can rapidly, accurately, and safely determine the presence or absence of ureteral obstruction. When obstruction is caused by ureterolithiasis, CT allows precise determination of stone size and location. These are the two most important factors used for patient management. In addition to direct stone visualization, there are many secondary CT signs of ureteral obstruction that are direct manifestations of the underlying pathophysiology. On the other hand, when obstruction is absent, CT can diagnose or exclude most other abnormalities that result in flank pain. As a result of its many advantages, unenhanced helical CT should become the dominant imaging modality for evaluation of all patients with acute flank pain in whom a clinical diagnosis is uncertain.

Acute Disease↗
PubMed1999

Acute and long-term stability studies of deoxy hemoglobin and characterization of ascorbate-induced modifications.

The reaction of ascorbate with recombinant hemoglobin (rHb1.1) in the presence of differing partial pressures of oxygen was studied. In the presence of 15 000 ppm (1.5%) residual oxygen, ascorbate/oxygen-mediated reactions resulted in an increased rate of autoxidation, modification of the beta-globin, increased oxygen affinity and decreased maximum Hill coefficient. One of the observed modifications to the beta-globin was a 72 Da addition to its N-terminus. Detailed characterization indicates the modification was an imidazolidinone type structure. Thorough deoxygenation of the hemoglobin solution to <150 ppm of oxygen prior to addition of ascorbate was required to prevent these modifications. Addition of ascorbate to the deoxy hemoglobin (deoxyHb) at pH 8 induced aggregation, eventually leading to precipitation. No such precipitation was observed at pH 7. Long-term storage of the hemoglobin was carried out by addition of ascorbate to deoxyHb at pH 7. The level of methemoglobin remained at <2% for up to 1 year at 4 degreesC, with no detectable precipitation of the protein. Modifications similar to those observed by the acute studies were observed over the 1-year period and correlated with disappearance of the added ascorbate.

Ascorbic Acid↗
PubMed1999

High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients.

Calcium (Ca) and magnesium (Mg) are involved in many processes related to depression. Evaluations of serum and plasma Ca and Mg levels in depressive disorders do not show consistent results. The few studies that examined their cerebrospinal fluid (CSF) levels tended to find no differences between depressed patients and controls. Because both hypercalcemia and hypomagnesemia are associated with depression, and as Mg may function as a Ca antagonist, it is suggested that the relationship between these cations could be different in depressed patients and controls. We examined CSF and serum Ca and Mg in acutely depressed patients diagnosed as having major depressive disorder or being in a depressive episode of bipolar disorder. Controls were subjects undergoing lumbar puncture as part of an evaluation for headache or suspected meningitis and found to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study. We further discuss our findings in their relation to the acuteness of the depressive disorders.

Acute Disease↗
PubMed1998

Cerebrospinal fluid inositol monophosphatase: elevated activity in depression and neuroleptic-treated schizophrenia.

BACKGROUND: Inositol monophosphatase (IMPase) is a key enzyme in the regulation of the activity of the phosphatidyl inositol (PI) signaling pathway. This enzyme is also found in the cerebrospinal fluid (CSF), where it may prove useful as a marker of dysfunctional PI signal transduction. METHODS: IMPase activity was measured in lumbar CSF of depressed and neuroleptic-treated schizophrenic patients. In addition, and to gain an insight into the factors that influence the levels of CSF IMPase, enzyme activity was measured in subgroups of schizophrenic patients treated for 3-7 days with lithium or 7 days with inositol. RESULTS: CSF IMPase activity was significantly increased by 88% in depressed and by 172% in schizophrenic patients relative to control subjects. Lithium produced a marked increase in CSF IMPase activity in the group as a whole, and this group effect could be more specifically attributed to 3 of the 8 individuals in whom enzyme activity increased by over 300%. On the other hand, inositol had no effect on CSF IMPase activity. CONCLUSIONS: In the absence of a clear relationship between CSF IMPase activity and neuronal PI signaling pathways it is not possible to correlate these changes with altered neuronal function. Nevertheless, increased CSF IMPase activity in depression and schizophrenia may be a marker of the pathophysiological processes underlying these disorders. Moreover, the large lithium-induced increase in IMPase activity seen in a subgroup of schizophrenic subjects suggests a differential regulation of CSF enzyme activity in these patients.

Antipsychotic Agents↗
PubMed1998

Identification of a nickel(II) binding site on hemoglobin which confers susceptibility to oxidative deamination and intramolecular cross-linking.

Complexation of Ni(II) with native state recombinant hemoglobin is shown to produce NH2-terminal deamination and globin cross-linking in the presence of the oxidant potassium peroxymonosulfate (OxoneTM). Both the oxidative deamination and cross-linking are exclusive to the beta chains. Recombinant hemoglobin mutants have been created to identify protein sequence requirements for these reactions. It was found that His-2 of the beta globin is required for redox active Ni(II) complexation, oxidative deamination, and cross-linking. The oxidative deamination results in the formation of a free carbonyl in place of the NH2-terminal amine of the beta chain. Most cross-linking of the beta globin occurs intramolecularly, forming beta globin dimers. Structural characterization of the beta globin dimers indicates the presence of heterogeneous cross-links within the central hemoglobin cavity between the NH2 terminus of one beta chain and the COOH-terminal region of the other.

Amino Acid Sequence↗
PubMed1998

Effects of oral contraceptives on free fatty acid metabolism in women.

These studies examined whether women using oral contraceptives have abnormalities in free fatty acid (FFA) metabolism compared with women not using oral contraceptives. Plasma palmitate kinetics ([3H]palmitate) were measured at rest, following glucose ingestion, and during epinephrine infusion in 13 oral contraceptive users and 13 matched women not using oral contraceptives. Oral contraceptive users had significantly greater plasma triglyceride concentrations and glucose responses to oral glucose tolerance testing. No differences in basal (2.1 +/- 0.1 v 1.8 +/- 0.2 micromol x kg fat-free mass x FFM(-1) x min[-1]), glucose-suppressed (0.6 +/- 0.1 v 0.5 +/- 0.1 micromol x kg FFM(-1) x min[-1]), or epinephrine-stimulated (3.3 +/- 0.1 v 3.6 +/- 0.2 micromol x kg FFM(-1) x min[-1]) palmitate flux were detected between women using and not using oral contraceptives. The respiratory quotient (RQ) also was not different between groups. We conclude that the increase in plasma triglycerides and the mild glucose intolerance seen with oral contraceptive use is not associated with significant abnormalities of FFA metabolism.

Adult↗
PubMed1998

Effect of inositol treatment on the behavior of rhesus monkeys: preliminary results.

1. The effects of inositol (20 g/day, oral) on spatial learning and spontaneous home-cage behavior of four Rhesus monkeys, were studied in a crossover design. 2. Results indicate no marked inositol effect on learning, memory, or behavior. There was a suggestion of an effect of chronic inositol in reducing cage-induced repetitive behavior as indicated by increased switching between modes of behavior, and reduction in length of longest behavioral about. Furthermore inositol may increase time spent in environmentally- rather than self-oriented behavior. 3. Previous behavioral studies of inositol were performed in rats, which maintain low brain inositol levels compared to primates, including humans. The present study demonstrates the feasibility of primate behavioral studies with inositol, and shows the need for longer time experiments and increased variety of behavioral tests.

Animals↗
PubMed1998

Utilization of valproate: extent of inpatient use in the New York State Office of Mental Health.

OBJECTIVE: To describe the extent and type of use of valproate among hospitalized psychiatric patients. METHOD: A database containing patient information and drug prescription information for every in-patient within the adult civil facilities of the New York State Office of Mental Health was queried. RESULTS: In 1994, 2,888 of 18,668 in-patients received valproate (15.5%). In 1996, 4,247 of 12,444 in-patients received valproate (34.1%). In 1996, approximately 50% of all patients diagnosed as bipolar or schizoaffective, and 28% of all patients diagnosed with schizophrenia, received valproate. Once started on valproate, over 90% remained on it after 2 weeks, with no difference found in the discontinuation rates between valproic acid or divalproex sodium at the end of the initial 14 day period. Patients received valproate for approximately two-thirds of their hospital stay, at a mean dose of 1400 mg/day. 95% also received concomitant antipsychotics, and 20% received concomitant lithium. Use of lithium and carbamazepine was less in 1996 than in 1994, but the magnitude of this change was much less than the increase in utilization of valproate. CONCLUSIONS: From 1994 to 1996 valproate use has more than doubled, and it is being used widely in patients with schizophrenia, an off-label indication for which there is only anecdotal support in the literature. Given the lack of difference in early discontinuation rates, there are probably no dramatic differences in side effects for the two preparations of valproate.

Adult↗
PubMed1998

Dopamine D4 receptor and serotonin transporter promoter in the determination of neonatal temperament.

Genetic effects on behavior were evaluated at a time in early development when we hypothesized that environmental influences are minimal and least likely to confound associations between temperament and genes. The behavioral effects of two common polymorphisms linked respectively in some, but not all, studies to novelty seeking (dopamine D4 receptor-D4DR) and neuroticism and harm avoidance (serotonin transporter promoter region-STPR) were examined in a group of 81 two-week-old neonates. Neonate temperament was evaluated using the Brazelton neonatal assessment scale (NBAS). Multivariate tests of significance showed a significant association of D4DR across four behavioral clusters pertinent to temperament including orientation, motor organization, range of state and regulation of state. A significant multivariate interaction was also observed between D4DR and STPR. The effect of the homozygous short STPR genotype (s/s) was to lower the orientation score for the group of neonates lacking the long form (L) of D4DR. When adult subjects were grouped by the STPR polymorphism there is no significant effect of L-D4DR in those subjects homozygous for the STPR short form (s/s) whereas in the group without the homozygous genotype the effect of L-D4DR is significant and accounts for 13% of the variance in novelty seeking scores between groups.

Anxiety↗
PubMed1998

Treatment of intractable pain with topical large-dose capsaicin: preliminary report.

UNLABELLED: Complex regional pain syndromes (CRPS) and neuropathic pain are often poorly controlled by conventional pharmacologic interventions. We administered 8-methyl-N-vanillyl-noneamide (capsaicin) at doses of 5%-10% to individuals with such disorders in this trial. Previous limitations to trials with larger-dose, topical concentrations of capsaicin included intense burning sensations experienced after application. To enable patients to tolerate the high concentrations, we first performed regional anesthesia. All patients reported at least some relief. Of 10 patients, 9 obtained substantial analgesia that lasted 1-18 wk. At Week 1 after therapy, the mean verbal analog scale (VAS) scores decreased from 8.0 to 3.0. At Week 4 after therapy, mean VAS score was 4.5. Analgesia lasted from < 1 wk (1 patient) to more than 50 wk (1 patient). Patients received one to eight treatments. With one exception, patients receiving more than one treatment obtained additional relief with subsequent treatment. Pain responsive to opioids was the only side effect of treatment. Large-dose capsaicin administered with regional anesthesia may effectively minimize refractory CRPS and neuropathic pain. A double-blind, placebo-controlled study in patients with bilateral peripheral neuropathy using epidural anesthesia with and without large-dose topical capsaicin is in progress. IMPLICATIONS: Sensory neuropathies are associated with many diseases. Pain from these disorders can produce greater disability than the primary disease processes themselves. Currently available therapies are limited. However, the intermittent application of large-dose topical capsaicin may provide significant pain relief, decrease chronic analgesic dependence, and decrease aggregate health care expenditures.

Administration, Topical↗
PubMed1998

Clinico-tremorgraphic features of neuroleptic-induced tremor.

Instrumental tremorgrams have been used to improve the diagnostic accuracy of various movement disorders, including tardive akathisia. The aim of the present work was to evaluate their place in the diagnosis of neuroleptic-induced tremor and to determine whether they can help to differentiate this disorder from other neuroleptic-induced movement disorders and from other types of tremor. Fourteen psychiatric patients treated with various neuroleptic medications were diagnosed as having neuroleptic-induced tremor on the basis of clinical criteria. They underwent accelerometric recordings following diagnosis. All patients demonstrated upper-limb tremor; four also had involvement of the lower limbs, jaw or tongue. Most demonstrated both resting and postural tremor, the latter being the more prominent. The tremor was mainly rhythmic, regular and sinusoidal. It did not significantly interfere with activities of daily living in the majority of patients, but four did exhibit some degree of impairment. Repeated accelerometric recordings showed constant and regular waveforms and frequencies (between 4 and 7 Hz) in each patient. We conclude that the presence of repeated constant waveforms and frequencies on accelerometric tracings may serve as confirmation of the diagnosis of neuroleptic-induced tremor. In light of the findings of this and other studies, we suggest that tremorgrams may be helpful in differentiating neuroleptic-induced tremor from other neuroleptic-induced movement disorders (e.g., tardive dyskinesia and tardive akathisia) and from psychogenic tremor. Although these techniques may also assist in the differentiation of neuroleptic-induced tremor from some tremor disorders (e.g., asterixis or ataxic tremor), their overall potential to distinguish it from other types of organic tremor is more limited.

Adult↗
PubMed1998

Fecal hydrogen sulfide production in ulcerative colitis.

OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.

Adolescent↗