Search PubMed⌕ Search

Biomedical subjects

M D Jibson

Publications and source records attributed to M D Jibson.

16 recordsLinked to original sources
PubMed2003

Efficacy of newer generation antipsychotics in the treatment of schizophrenia.

The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy between risperidone, olanzapine, and quetiapine, there are clear differences in their side-effect profiles and these are briefly summarized.

Antipsychotic Agents↗
PubMed2001

A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study.

BACKGROUND: The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice. OBJECTIVE: The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms. METHODS: This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D). RESULTS: A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028). CONCLUSIONS: The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.

Adolescent↗
PubMed2001

Pharmacologic treatment of schizophrenia: what the future holds.

The advent of the newer "atypical" antipsychotics has revolutionized pharmacologic treatment of schizophrenia (SZ) and other psychotic disorders. In contrast to the first-generation conventional neuroleptics, these second-generation antipsychotic agents possess a broader spectrum of efficacy and cause fewer motor side effects such as extrapyramidal symptoms and tardive dyskinesia. Despite their substantial advantages, however, these second-generation agents also have significant limitations in terms of both efficacy and adverse effects. Several strategies to address these shortcomings are currently under study and some of these are likely to become part of our therapeutic armamentarium in the future. Current shortcomings in the pharmacologic treatment of SZ and strategies under investigation to address each of these deficiencies are reviewed. New formulations of existing medications and new antipsychotics under development are discussed. Developing adjunctive treatment strategies to address each of the major psychopathologic domains in SZ are summarized. The potential application of genetic information to treatment-matching in SZ is reviewed and likely refinements in the practice of evidence-based medicine in the pharmacotherapy of SZ are considered.

Journal Article↗
PubMed1999

Antipsychotics from theory to practice: integrating clinical and basic data.

The recent introduction of the atypical antipsychotics into the treatment arena for psychoses and related disorders comes with justifiable excitement. These newer antipsychotics offer several clinical benefits over the conventional antipsychotics, which have been the mainstays of care thus far. The primary advantage of these atypical agents is their superior side effect profiles, particularly with regard to extrapyramidal side effects (EPS). The implications from a reduction in EPS touch on virtually every aspect of pathology in schizophrenic illness, including short- and long-term movement disorders, negative symptoms, noncompliance, cognitive dysfunction, and dysphoria. It should be emphasized that while atypical antipsychotics share many clinical attributes, there are also substantial differences among them. This review will examine the pharmacology, clinical efficacy, and side effect profiles of the atypical antipsychotics and attempt to relate the attributes observed in clinical practice and clinical trials to their basic pharmacologic profiles. There is a fair, but not perfect, correspondence between the pharmacologic profiles of the different atypical antipsychotics and their respective clinical attributes. After a comparative overview of their receptor-binding profiles, a brief pharmacokinetic summary will be provided. Finally, the clinical profiles of these agents will be summarized with regard to both their efficacy and adverse effects.

Animals↗
PubMed1995

Tinnitus and ECT.

We report the case of a 69-year-old man with major depressive disorder and occupational tinnitus; both problems were refractory to several different treatment modalities, but were successfully treated with electroconvulsive therapy (ECT). The tinnitus was present for 15-20 years, but had worsened during the 3 years before treatment, causing him significant distress. Extensive organic workup did not identify a treatable etiology for his symptoms. To date, he has been hospitalized four times due to depressive symptoms associated with tinnitus. He has received ECT each time, and has responded well on each occasion.

Aged↗
PubMed1983

Purification and properties of protease F, a bacterial enzyme with chymotrypsin and elastase specificities.

It has been previously demonstrated that commercial bacterial fibrinolysin (EC 3.4.21.7) selectively cleaves the bond between Met-53 and Ala-54 in ovine prolactin (199 amino acids). A one-step purification procedure on DEAE-cellulose for Protease F, which is the active component of bacterial fibrinolysin, and properties of the purified enzyme are reported. The enzyme is homogeneous as judged by acrylamide gel electrophoresis. Its molecular weight, calculated from gel filtration experiments on Sephadex G-100, is around 13,800. Amino acid analyses do not reveal the presence of any half-cystines. The presence of one tryptophan residue per enzyme molecule was resolved from the fluorescence spectrum. Amino terminal analysis showed that leucine was at the amino terminal position. Protease F hydrolyzes casein and synthetic specific substrates for chymotrypsin and elastase esterases but not for trypsin esterases. It is fully inhibited by phenylmethylsulfonyl fluoride, by chicken ovoinhibitor, and by Chymotrypsin Inhibitor I from potatoes but not by the trypsin-chymotrypsin inhibitors from soybeans and chick peas or by tosyl-L-phenylalanine chloromethyl ketone. The enzyme is stable at room temperature and in the cold, it is not affected by dialysis or by freezing and thawing, but it is inactivated during freeze-drying. The circular dichroism spectra of Protease F indicate an approximate 20% alpha-helix content of the enzyme with a considerable similarity to those of subtilisin, elastase, and beta-trypsin. The relatively low molecular weight of Protease F, the absence of intrachain disulfide bridges, and the fact that it is inhibited by several, but not all, chymotrypsin inhibitors suggest that it may differ phylogenetically from the known serine proteases.

Amino Acids↗
PubMed1982

Human somatotropin. Selective removal with trypsin of residues 135-145 from the hormone molecule with no loss of biological activities.

A 11-residue segment, sequence positions 135-145, has been cleaved selectively from the human somatotropin molecule by limited digestion of the hormone with trypsin at pH 6.0 in 90% (v/v) glycerol. Differences between the tertiary structures of the native and trypsin-modified hormones have been demonstrated by circular dichroism spectroscopy. Despite these conformational differences, the biological properties of intact hormone and its modified form appeared to be very similar, as tested by two receptor-binding assays, radioimmunoassay, and the rat tibia test.

Amino Acid Sequence↗
PubMed1981

Two contiguous thrombin fragments of human somatotropin form a functionally active recombinant, but the two homologous fragments from sheep hormone do not.

Two thrombin fragments of reduced-carbamidomethylated human somatotropin representing the full primary structure of the native hormone (residues 1-134 and 135-191) have been found to form a recombinant molecule with properties similar to those of reduced-carbamidomethylated human somatotropin as shown by circular dichroism spectroscopy, two receptor-binding assays, and radioimmunoassay. In contrast, the homologous thrombin fragments of reduced-carbamidomethylated sheep hormone (residues 1-133 and 134-191) do not undergo recombination. Furthermore, neither the reduced-alkylated nor the reduced and nonalkylated C-terminal thrombin fragment of sheep hormone is able to interact with the reduced-carbamidomethylated N-terminal thrombin fragment of human hormone, under conditions which favor the recombination of the two human somatotropin fragments.

Amino Acid Sequence↗
PubMed1981

Ovine prolactin: equilibrium characteristics of the recombinant molecule formed by noncovalent interaction of two fibrinolysin fragments by fluorescence polarization.

The equilibrium characteristics of the recombined molecule formed by noncovalent interaction of two fibrinolysin fragments of ovine prolactin (oPRL) have been studied with fluorescence polarization. Fluorescein isothiocyanate (isomer I) was used to label oPRL-(1-53), creating a fluorescent peptide indistinguishable from the unlabeled fragment in the complementation reaction with oPRL-(54-199). The dissociation constant of the recombinant prolactin was 0.144 microM at 30 degrees C, with a free energy of dissociation of 9.50 kcal/mol.

Animals↗
PubMed1981

beta-Endorphin. Circular dichroism of synthetic human analogs with various chain lengths in methanol solutions.

The alpha-helix content of human beta-endorphin (beta h-EP) has been determined by circular dichroism (CD) in solutions ranging from 0 to 95% methanol in water. In addition, the CD spectra of beta h-EP-(1-30),-(1-29),-(1-28),-(1-27),-(1-26),-(1-21) and -(1-15) have been examined in 90% methanol, and their alpha-helix contents estimated using parameters determined for this solvent. Addition of methanol to beta h-EP solutions brings about a noncooperative formation of alpha-helix. An attempt to correlate secondary structure in methanol with biological and immunological activities showed limited direct correspondence, but may indicate the involvement of the tertiary interactions.

Amino Acid Sequence↗
PubMed1980

Circular dichroism spectra of cleavage fragments of soybean trypsin-chymotrypsin inhibitor.

Circular dichroism spectra of biologically active fragments of Bowman-Birk soybean inhibitor have been determined in acidic, neutral, and alkaline conditions. Neither fragment showed evidence of alpha-helix or beta-structure. Negative dichroism above 260nm has been assigned in both fragments primarily to disulfide bonds, with a minor contribution from tyrosine in a hydrophilic environment. The individual spectra of these fragments, and their sum between 230 and 340 nm have been compared with the spectra of the intact inhibitor and several structurally related proteins. Possible interactions which may give rise to CD bands in this region are discussed.

Chymotrypsin↗
PubMed1979

Secondary structure prediction of anterior pituitary hormones. Lack of correlation between predicted values and circular dichroism data.

The secondary structures of human somatotropin, human choriomammotropin, ovine and porcine prolactin, human, ovine and porcine beta-lipotropin, human and ovine lutropin, human thyrotropin, human corticotropin, alpha-melanotropin and human beta-melanotropin have been predicted by the method of Chou & Fasman. Predicted contents of alpha-helix and beta-sheet do not correspond well with values estimated from circular dichroism spectra.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

New atypical antipsychotic medications.

Conventional antipsychotics were the first treatments effective in controlling psychotic symptomatology and revolutionized management of psychotic disorders when introduced in the 1950's. The use of these agents has, however, been marked by several shortcomings, including limited efficacy in treating the negative and cognitive symptoms of schizophrenia, and by significant extrapyramidal and other side-effects. There appears to be justifiable excitement about the introduction of the newer atypical antipsychotics, which may represent the second pharmacological revolution in the treatment of psychotic disorders. But how are these agents really different from their neuroleptic predecessors? How is their pharmacological profile different? Are there clear differences in efficacy? How do side-effect profiles differ? These issues are reviewed in this manuscript. Atypical agents are pharmacologically distinct from their neuroleptic predecessors. Their primary advantage is their superior side effect profiles, particularly with regard to EPS. The implications of EPS reduction touch virtually every domain of pathology in schizophrenia, including short- and long-term movement disorders, negative symptoms, noncompliance, relapse rate, cognitive dysfunction, and dysphoria. It should be emphasized that while atypical antipsychotics share some clinical attributes, there are substantial clinical differences between them as well. These differences are reviewed in this article as well. The drugs' unique profiles with regard to other side effects may make it possible to tailor treatment more individually to patients. Further refinement of our understanding of the clinical utility of these drugs awaits their widespread use in mainstream clinical settings. Controlled studies comparing them to one another should be of particular interest.

Antipsychotic Agents↗