Biomedical subjects

Paola Salvatore

Publications and source records attributed to Paola Salvatore.

At least 19 recordsLinked to original sources

PubMed2006

Expression of recombinant puroindolines for the treatment of staphylococcal skin infections (acne vulgaris).

Puroindolines are antimicrobial peptides that occur in wheat seed, and are characterized by broad antimicrobial activity. We describe the heterologous expression of puroindoline A and B in the Origami strain of Escherichia coli. The recombinant puroindolines showed the same antimicrobial activity on Staphylococcus epidermidis as compared to the native peptides (MIC(90)=30microgml(-1)). The bactericidal activity was 125microgml(-1) for recombinant puroindoline A and 42microgml(-1) for recombinant puroindoline B. Neither protein shows in vitro haemolytic activity or toxicity towards the murine macrophage cell line J774, but they are able to kill intracellular staphylococci. Our preliminary results suggest that recombinant puroindolines deserve further attention as alternatives to the conventional antibiotics in the control of S. epidermidis skin infections.

Acne Vulgaris↗

PubMed2006

RecB-dependent mutator phenotype in Neisseria meningitidis strains naturally defective in mismatch repair.

Several invasive serogroup B meningococcal strains phylogenetically related to the lineage III (ET-24) exhibited a mutator phenotype as shown by mutagenicity assay using rifampicin-resistance as a selection marker. Hypermutation was associated to the presence of defective mutL alleles that were genetically characterized. Interestingly, the mutator phenotype was suppressed when a non-functional recB(ET-37) allele, derived from ET-37 meningococcal strains, replaced the functional recB allele in a lineage III strain. In contrast, the same gene replacement did not affect mutation frequencies in a mismatch repair-proficient strain. These results suggested that in MutL-deficient strains spontaneous mutations mostly arise from post-replicative DNA synthesis associated to the activity of the RecBCD recombination pathway.

Adenosine Triphosphatases↗

PubMed2006

Utility of the temperament and character inventory (TCI) in outcome prediction of laparoscopic adjustable gastric banding: preliminary report.

BACKGROUND: Research about personality factors involved in successful outcome after bariatric surgery has led to contrasting results. The reasons for such discrepancies may include the lack of assessment of adaptive personality traits and of psychiatric co-morbidity, which may limit the reliability of personality findings. This study aimed to provide exploratory data regarding preoperative personality dimensions and weight loss prediction 1 year after laparoscopic adjustable gastric banding (LAGB). Both normal and deviant personality patterns were assessed by means of the Temperament and Character Inventory (TCI). Moreover, co-morbid psychiatric disturbances were evaluated both categorically and dimensionally. METHODS: 65 morbidly obese subjects applying for LAGB were evaluated preoperatively by means of the TCI, standardized diagnostic interview, rating scales and questionnaires to assess co-morbid psychopathology. After intake screening, 35 subjects (mean age 41.2, mean BMI 45.5) were accepted for and underwent LAGB. BMI reduction 1 year following LAGB was used as an outcome measure and entered as a dependent variable in a stepwise multiple regression analysis. TCI scores, presence and severity of eating, depressive and anxiety disorders, sex, age, level of education and BMI at baseline were tested as independent variables. RESULTS: Preoperative TCI 'Persistence' scores explained >40% of variance of BMI reduction 1 year following LAGB, irrespective of preoperative BMI, age, gender, educational level, psychiatric co-morbidity, psychopathology severity and other temperament and character features. CONCLUSIONS: Some personality dimensions, as measured by the TCI, may be involved in successful weight control after LAGB.

Adult↗

PubMed2005

Antipsychotic drug use: McLean Hospital, 2002.

OBJECTIVE: Major changes in antipsychotic treatment in recent years encouraged a survey of inpatient practice in 2002, compared with earlier samples. METHODS: Based on records of a random sample of McLean Hospital inpatients prescribed antipsychotics in 2002, the study recorded DSM-IV discharge diagnosis, all psychotropic treatments and doses, initial, peak and final doses of all antipsychotics, clinical status at admission and discharge, and adverse effects reported. Results were compared with similar data from our earlier surveys. RESULTS: Subjects were 344 inpatients (n = 202 women, 59%), diagnosed with psychotic (n = 102, 30%), bipolar (n = 93, 27%), major depressive (n = 67, 19.5%), dementia (n = 19, 5.5%), substance-use (n = 28, 8%) or other psychiatric disorders (n = 35, 10%). Second-generation antipsychotics accounted for 88% of antipsychotic prescriptions; 17% of patients received > or = 2 antipsychotics and total CPZ-eq discharge does in 2002 averaged 291 +/- 305 mg/day (22% less than a 1998 peak). Doses were unrelated to age, but higher in men, among psychotic vs major affective disorder patients, and with greater illness-severity and longer hospitalization. There was a 3.3-fold increase in the simultaneous use of > or = 3 psychotropic agents since 1998. CONCLUSIONS: The use of second-generation antipsychotics dominates current inpatient practice. Total antipsychotic dosing has not increased recently, but the use of multiple psychotropics increased strikingly from 1998 to 2002.

Adult↗

PubMed2005

Use of combinations of antipsychotics: McLean Hospital inpatients, 2002.

BACKGROUND: The empirical use of combinations of antipsychotic agents appears to be increasing with little research support for the relative efficacy, safety or cost-effectiveness of this practice. Such treatment was evaluated in hospitalized psychiatric patients. METHODS: Samples of consecutive inpatients treated with > or = 2 ('polytherapy') vs 1 antipsychotic ('monotherapy') were matched on age, sex, diagnosis and admission clinical ratings, and these groups were compared on total daily chlorpromazine-equivalent doses, days in hospital, and changes in clinical ratings between admission and discharge. RESULTS: The study sample included 69 polytherapy and 115 well-matched monotherapy subjects. Despite matching for initial CGI and GAF ratings, polytherapy was associated with high PANSS subscale scores of positive symptoms among affective psychosis, and relatively greater PANSS subscale ratings of excitement-agitation among patients diagnosed with schizophrenia. Estimated clinical improvement during hospitalization was similar among poly- and monotherapy patients, but total daily CPZ-eq doses at discharge averaged twice-greater with polytherapy, and hospitalization lasted 1.5 times longer. CONCLUSIONS: Antipsychotic polytherapy as well as the types of agents combined may reflect clinician responses to particular symptom patterns. The value of specific combinations of antipsychotic agents and their comparison with monotherapies requires specific, prospective, randomized and well-controlled trials that consider matching on clinical characteristics and truly comparable doses across regimens.

Adult↗

PubMed2005

Aripiprazole: initial clinical experience with 142 hospitalized psychiatric patients.

BACKGROUND: Aripiprazole is the first dopamine D2 receptor partial-agonist approved for treatment of schizophrenia. Its apparently benign adverse-effect profile encourages broader use in other disorders, especially to limit weight gain associated with other antipsychotic or antimanic agents. We considered the first 6 months of experience with aripiprazole in psychiatric inpatients with a range of disorders. METHODS: We analyzed data obtained from medical records of patients treated with aripiprazole who were hospitalized at McLean Hospital (for 19 +/- 18 days) between December 2002 and June 2003 to evaluate dosing, tolerability, and clinical effects of this new agent in patients diagnosed with DSM-IV psychotic, major affective, or other disorders. RESULTS: Out of a sample of 2766 adult inpatients (65.5% women), 142 were given aripiprazole (mean final daily dose, 16.1 +/- 6.2 mg, 0.20 +/- 0.09 mg/kg body weight) for major affective disorders (52%), primary psychotic disorders (40%), and dementia (8%). CGI ratings improved by 20% on average. Adverse effects were infrequent (15.5%), were three times more likely among women, and most often involved moderate behavioral activation or nausea, with no new episodes of mania. Of the patients who were given aripiprazole, 83% continued it at discharge. Many patients were obese when they were admitted, and obesity was associated with relatively low mg/kg doses of aripiprazole. CONCLUSIONS: Aripiprazole was used in a range of disorders and was generally well tolerated. Adverse effects may reflect its unique dopamine partial-agonist activity. Since aripiprazole is likely to be considered for obese patients, body weight should be considered in establishing adequate doses. Controlled trials of this antipsychotic agent in disorders other than schizophrenia are needed.

Adult↗

PubMed2005

Substance abuse in first-episode bipolar I disorder: indications for early intervention.

OBJECTIVE: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder. METHOD: The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods. RESULTS: Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes. CONCLUSIONS: Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.

Adult↗

PubMed2004

On the periodicity of manic-depressive insanity, by Eliot Slater (1938): translated excerpts and commentary.

Since the classic descriptions of the course of bipolar and recurrent depressive forms of manic-depressive illness by Emil Kraepelin a century ago, it has been considered a truism that the rate of cycling increases, and wellness intervals shorten, with rising counts of recurrences, particularly early in the natural history of the illness. Less well known is that the analysis of this phenomenon is vulnerable to a computational artifact first described by Eliot Slater, based on his reanalysis of data from manic-depressive patients first evaluated by Kraepelin at the Munich Psychiatric Institute. Slater realized that there is an increasingly disproportionate representation of faster-cycling patients in sub-samples involving higher cycle-counts in pooled samples of subjects. More accurate results require analyzing illness-course either within individuals, or in groups matched for episode-counts. This artifact is pervasive in the older and modern research literature, but still not widely recognized. Since Slater's 1938 report in German is not well known, we provide an abbreviated English translation with commentary and additional reanalysis to highlight the phenomenon that might be termed 'Slater's Fallacy'.

Bipolar Disorder↗

PubMed2004

Ziprasidone: first year experience in a hospital setting.

BACKGROUND: The antipsychotic drug ziprasidone, FDA-approved and introduced in the United States in February 2001 for the treatment of schizophrenia, appears to have similar efficacy but better tolerability than older antipsychotics and requires further evaluation under clinical conditions. METHODS: We analyzed medical records of McLean Hospital inpatients treated with ziprasidone between March 2001 and February 2002, gathering data on DSM-IV diagnoses, presenting symptoms, dosing, concomitant psychotropic medications, clinical changes, adverse effects, and electrocardiographic (ECG) findings. RESULTS: Ziprasidone was given to 151 inpatients (3.4% of admissions; 108 women, 43 men), aged 37.5 +/- 11.4 years, who presented with depression (n = 79), psychosis (n = 46), mania (n = 18), bipolar mixed-states (n = 4), or other conditions (n = 4). Daily doses averaged 49.8 +/- 34.1 mg initially and 83.2 +/- 46.3 mg at discharge; the greatest dose increases during hospitalization (by a mean of 61%) were in patients with schizoaffective disorder (n = 46; 30% of cases). In 41 cases (27%), ziprasidone was the only antipsychotic at discharge; in 61 (40%) it was used with other antipsychotics. Ziprasidone was discontinued during hospitalization in 49 cases (32.5%), due to lack of efficacy (n = 26; 17.2%), adverse effects (n = 13, 8.6%), or reasons not stated (n = 10, 6.6%). Of 70 patients for whom ECG data were obtained during treatment with ziprasidone, 8 (11%) had QTc intervals > 450 msec during treatment, but none of the 39 patients with ECGs both before and during ziprasidone treatment showed clinically meaningful increases in QTc intervals. Ziprasidone was discontinued in 4 patients (2.6%) due to concern about QTc intervals, but in no case was the QTc interval > or = 500 msec or associated with clinical cardiac toxicity. Improvements in CGI and GAF scores from admission to discharge were similar across diagnoses and unrelated to length of stay or ziprasidone dose. CONCLUSIONS: Ziprasidone was well tolerated by hospitalized patients with various major psychiatric disorders and may be of value in conditions other than schizophrenia.

Adult↗

PubMed2004

Regulation and differential expression of gdhA encoding NADP-specific glutamate dehydrogenase in Neisseria meningitidis clinical isolates.

Meningococcal gdhA, encoding the NADP-specific l-glutamate dehydrogenase (NADP-GDH), is essential for systemic infection in an infant rat model. In this paper, a limited transcriptional analysis detected differences in gdhA expression among clinical isolates. In strains expressing high levels of gdhA mRNA, two promoters, gdhA P1 and gdhA P2, initiated transcription of gdhA. In contrast, in strains expressing low mRNA levels, gdhA P2 was not active because of weak expression of gdhR, an associated regulatory gene. Gene knock-out and complementation of a gdhR-defective mutant confirmed that GdhR is a positive regulator for gdhA P2. Trans-activation of gdhA P2 was maximal in complex medium during late logarithmic growth phase and in chemical defined medium (MCDA) when glucose (MCDA-glucose) instead of lactate (MCDA-lactate) was used as a carbon source in the presence of glutamate. gdhR knock-out mutants lost both growth phase and carbon source regulation, and exhibited a growth defect more severe in MCDA-glucose than in MCDA-lactate. DNA-protein interaction studies demonstrated that 2-oxoglutarate, a product of the catabolic reaction of the NADP-GDH and an intermediate of the tricarboxylic acid (TCA) cycle, inhibits binding of GdhR to gdhA P2.

Animals↗

PubMed2004

Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits.

OBJECTIVE: Since use of multiple drugs to treat psychiatric patients is increasing, and research on this practice is rare, the authors carried out a retrospective case-control study of multiple versus single antipsychotic treatment in psychiatric inpatients. METHOD: Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex, diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge. RESULTS: Initial doses were closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5 days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were similar (within 11%) for both treatments. CONCLUSIONS: Short-term treatment with multiple antipsychotics was associated with major increases in drug exposure, adverse events, and time in the hospital but with no apparent gain in clinical benefit. These findings require further testing in controlled prospective studies.

Adult↗

PubMed2003

The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence.

OBJECTIVE: Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania. METHOD: Bipolar disorder patients (N=166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score </=5 and Hamilton Depression Rating Scale score </=8), and functional (regaining of premorbid occupational and residential status). Rates of remission (syndromal recovery sustained >/=8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed. RESULTS: By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse. CONCLUSIONS: Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors.

Adolescent↗

PubMed2003

Pilot comparison of extended-release and standard preparations of divalproex sodium in patients with bipolar and schizoaffective disorders.

OBJECTIVE: The authors compared the new extended-release and standard preparations of divalproex sodium. METHOD: Twelve patients with DSM-IV bipolar disorder or schizoaffective disorder who were clinically stable while taking the standard form of divalproex participated in the study. These patients were given a single daily dose of the extended-release preparation of divalproex in an open 6-week trial. Clinical symptoms and adverse effects were rated weekly. Doses were adjusted to maintain steady serum valproate concentrations. RESULTS: The medication change was associated with negligible changes in clinical status and tolerability. To maintain serum drug levels, however, 21% higher doses of the extended-release preparation were required. CONCLUSIONS: Use of extended-release divalproex once a day was as well tolerated as the standard preparation, with no change in efficacy within 6 weeks, but the daily dose needed to maintain stable serum valproic acid concentration was 21% higher.

Ambulatory Care↗

PubMed2003

Cyclothymia, a circular mood disorder.

Ewald Hecker (1843-1909) was a collaborator of Karl Ludwig Kahlbaum (1828-1899). Both worked outside the university and public mental institutions of Germany. By meticulously observing clinical signs and illness-course, they laid the groundwork for modern descriptive psychiatry. Their clinical approach influenced Kraepelin and continues to dominate psychiatric classification. Hecker popularized several of Kahlbaum's syndromal concepts, including hebephrenia. Another was cyclothymia, a relatively benigh form of manic-depressive illness, introduced by Kahlbaum, in 1882. It included depressive (dysthymia), hypomanic (hyperthymia), and mixed hypomanic-depressive phases. The Kahlbaum-Hecker syndrome of cyclothymia survives in DSM-IV bipolar II disorder and cyclothymia. An annotated English translation of Hecker's 1898 paper is provided, with historical notes on Hecker and the significance of his work.

Cyclothymic Disorder↗

PubMed2002

Galectin genes: regulation of expression.

In this review we have summarized the more recent studies on the expression of mammalian galectins. One interesting observation that can be made is that in most of microarrays and/or differential display analysis performed in recent years one or more galectins have been picked up. From a critical evaluation of the pertinent studies the main conclusion that can be drawn is that, although it is not yet clear whether the 14 galectins identified so far have functions in common, a striking common feature of all galectins is the strong modulation of their expression during development, differentiation stages and under different physiological or pathological conditions. This suggests that the expression of different galectins is finely tuned and possibly coordinated. In spite of these observations it is rather unexpected that very few studies have been performed on the molecular mechanisms governing the activity of galectin genes.

Animals↗

PubMed2002

Phenotypes of a naturally defective recB allele in Neisseria meningitidis clinical isolates.

Neisseria meningitidis strains belonging to the hypervirulent lineage ET-37 and several unrelated strains are extremely UV sensitive. The phenotype is consequent to the presence of a nonfunctional recB(ET-37) allele carrying multiple missense mutations. Phenotypic analysis has been performed with congenic meningococcal strains harboring either the wild-type recB allele or the recB(ET-37) allele. Congenic recB(ET-37) meningococci, in addition to being sensitive to UV, were defective both in repair of DNA lesions induced by UV treatment and, partially, in recombination-mediated transformation. Consistently, the wild-type, but not the recB(ET-37), allele was able to complement the Escherichia coli recB21 mutation to UV resistance and proficiency in recombination. recB(ET-37) meningococci did not exhibit higher frequencies of spontaneous mutation to rifampin resistance than recB-proficient strains. However, mutation rates were enhanced following UV treatment, a phenomenon not observed in the recB-proficient counterpart. Interestingly, the results of PCR-based assays demonstrated that the presence of the recB(ET-37) allele considerably increased the frequency of recombination at the pilin loci. The main conclusion that can be drawn is that the presence of the defective recB(ET-37) allele in N. meningitidis isolates causes an increase in genetic diversity, due to an ineffective RecBCD-dependent DNA repair and recombination pathway, and an increase in pilin antigenic variation.

Alleles↗

PubMed2002

Inpatient antipsychotic drug use in 1998, 1993, and 1989.

OBJECTIVE: Patterns of clinical use of antipsychotic agents have changed greatly in the past decade. The authors' goal was to examine these patterns. METHOD: They evaluated medication use in all McLean Hospital inpatients treated with antipsychotic drugs during 3 months in 1998 (N=349) and compared the results with McLean Hospital inpatients treated with antipsychotics in 1993 (N=299) and Boston area inpatients in 1989 (N=50). RESULTS: The most commonly prescribed antipsychotics in 1998 were atypical agents; olanzapine was prescribed more often than risperidone or quetiapine, which were prescribed more often than other antipsychotics. Two or more antipsychotics were prescribed at some time during their hospitalization for 150 (43%) of the patients in 1998. The total discharge dose in chlorpromazine equivalents for the 349 patients for whom antipsychotics were prescribed at discharge was 371 mg/day, 29% higher than the total discharge dose for patients in 1993 and 46% greater than the dose in 1989. The dose of antipsychotics was greater for patients with psychotic illnesses than for those with affective illnesses. Higher doses were associated with greater clinical improvement, polypharmacotherapy, and younger patient age. CONCLUSIONS: Emerging trends toward higher total antipsychotic doses and polypharmacotherapy require critical assessments of cost-benefit relationships.

Adolescent↗

PubMedDate not supplied

Weygandt's On the Mixed States of Manic-Depressive Insanity: a translation and commentary on its significance in the evolution of the concept of bipolar disorder.

Wilhelm Weygandt's Uber die Mischzustände des manisch-depressiven Irreseins (On the Mixed States of Manic-Depressive Insanity) describes and conceptualizes mixed states of mood, behavior, and thinking commonly found in manic-depressive disorders. These ideas emerged from Weygandt's service in the 1890s at the Psychiatric Clinic of the University of Heidelberg, directed by Emil Kraepelin. In the sixth (1899) edition of Kraepelin's influential textbook, the concept of manic-depressive illnesses underwent a fundamental shift from a complex group of syndromal subtypes to a single integrated disorder, widely known from the 1921 English translation of the eighth (1920) edition. In the 1899 edition, Kraepelin acknowledged Weygandt for a new section on mixed manic-depressive states within the new integrated view of manic-depressive disorder. We provide biographical notes on Weygandt, a little-known but historically important figure, as well as the first English translation of his monograph and interpretive summaries of his findings. We also consider whether Weygandt's important insight that the same person could be both manic and depressed not only at different times but even at the same time served as an important stimulus to Kraepelin's unified manic-depressive disorder concept, which survives as bipolar disorder a century later.

Bipolar Disorder↗