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Biomedical subjects

J Silverman

Publications and source records attributed to J Silverman.

At least 55 records · Page 3Linked to original sources

A simple breathing circuit minimizing changes in alveolar ventilation during hyperpnoea.

Many clinical and research situations require maintenance of isocapnia, which occurs when alveolar ventilation (V'A) is matched to CO2 production. A simple, passive circuit that minimizes changes in V'A during hyperpnoea was devised. It is comprised of a manifold, with two gas inlets, attached to the intake port of a nonrebreathing circuit or ventilator. The first inlet receives a flow of fresh gas (CO2=0%) equal to the subject's minute ventilation (V'E). During hyperpnoea, the balance of V'E is drawn (inlet 2) from a reservoir containing gas, the carbon dioxide tension (PCO2) approximates that of mixed venous blood and therefore contributes minimally to V'A. Nine normal subjects breathed through the circuit for 4 min at 15-31 times resting levels. End-tidal PCO2 (Pet,CO2) at rest, 0, 1.5 and 3.0 min were (mean+/-SE) 5.1+/-0.1 kPa (38.1+/-1.1 mmHg), 4.9+/-0.1 kPa (36.4+/-1.1 mmHg), 5.0+/-0.2 kPa (37.8+/-1.6 mmHg) and 5.0+/-0.2 kPa (37.6+/-1.4 mmHg) (p=0.53, analysis of variance (ANOVA)), respectively; without the circuit, Pet,CO2 would be expected to have decreased by at least 2.7 kPa (20 mmHg). Six anaesthetized, intubated dogs were first ventilated at control levels and then hyperventilated by stepwise increases in either respiratory frequency (fR) from 10 to 24 min(-1) or tidal volume (VT) from 400 to 1,200 mL. Increases in fR did not significantly affect arterial CO2 tension (Pa,CO2) (p=0.28, ANOVA). Only the highest VT decreased Pa,CO2 from control (-0.5 +/- 0.3 kPa (-3.4 +/- 2.3 mmHg), p<0.05). In conclusion, this circuit effectively minimizes changes in alveolar ventilation and therefore arterial carbon dioxide tension during hyperpnoea.

Adult↗

Regional cerebral blood flow during the Wisconsin Card Sort Test in schizotypal personality disorder.

Regional cerebral blood flow (rCBF) was measured by single photon emission computed tomography in 10 patients with schizotypal personality disorder (SPD) and nine age- and sex-matched normal volunteers. Subjects performed both the Wisconsin Card Sort Test (WCST) and a control task, the Symbol Matching Test (SMT). Four-way analyses of variance were performed to assess relative rCBF of the prefrontal cortex and of the medial temporal region. Normal volunteers showed more marked activation in the precentral gyrus, while SPD patients showed greater activation in the middle frontal gyrus. Relative flow in the left prefrontal cortex was correlated with better WCST performance in normal volunteers. SPD patients, however, showed no such correlations in the left prefrontal cortex, but demonstrated correlations of good and bad performance with CBF in the right middle and inferior frontal gyrus, respectively. Thus, at least some SPD patients demonstrate abnormal patterns of prefrontal activation, perhaps as a compensation for dysfunction in other regions.

Adult↗

Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging.

Magnetic resonance imaging (MRI) was performed in 12 patients with schizotypal personality disorder (SPD), 11 patients with chronic schizophrenia, and 23 age- and sex-matched normal volunteers. MRI slices were acquired in the axial plane at 1.2-mm intervals, and the ventricles were traced on every other slice. The lateral ventricular system was divided into the anterior horn, temporal horn, and dorsal lateral ventricle. Schizophrenic patients had larger left anterior and temporal horns than the normal volunteers. Size of the left anterior and temporal horn in SPD patients was intermediate between those of normal volunteers and schizophrenic patients and differed significantly from schizophrenic patients. The left-minus-right difference was larger in schizophrenic patients than in normal volunteers or SPD patients. Thus, in their structural brain characteristics, as well as in their clinical symptomatology, SPD patients evidence, in attenuated form, abnormalities resembling those found in full-fledged schizophrenia. The findings suggest that decreased left hemispheric volume, in frontal and temporal regions, may characterize both psychotic and non-psychotic disorders of the schizophrenia spectrum.

Adult↗

Serotonergic function and self-injurious behavior in personality disorder patients.

Self-directed aggression, whether in the form of non-suicidal self-mutilation or suicidal behavior, is a prominent feature of personality disorders. We hypothesized that self-injurious behavior, like suicidal behavior, represents a form of self-directed aggression, and may, like suicidal behavior and impulsive aggression, be associated with a decrease in central serotonin function in personality disorder patients. Ninety-seven patients with DSM-III personality disorder underwent D,L-fenfluramine challenge as an assessment of serotonergic activity. Patients with a history of self-mutilation or suicide had blunted prolactin and cortisol responses to D,L-fenfluramine compared to those with neither, and those with both had the most blunted responses to fenfluramine. These data raise the possibility that the central 5-HT abnormality, previously associated with suicidal behavior, may be associated with self-directed violence and not necessarily specifically with suicidal intent.

Adult↗

Depressive response to physostigmine challenge in borderline personality disorder patients.

The purpose of this study was to examine the relationship between mood and hormonal responses to cholinergic challenge with physostigmine in order to assess cholinergic system responsiveness in borderline personality disorder (BPD) patients, other non-BPD personality disorder patients, and normal controls. Thirty-four personality disorder patients, 10 of whom met criteria for BPD and 24 of whom met criteria for other, non-borderline, personality disorders, and 11 normal controls participated in a double blind, placebo controlled physostigmine challenge paradigm. The Profile of Mood States depression subscale (POMS-D) self report measure was obtained at baseline and following the physostigmine or placebo infusions. A repeated measures ANOVA of POMS-D scores in placebo and drug conditions indicated a significantly greater depressive response in the total cohort of personality disorder patients than in the normal comparison group (p < 0.05). However, the depressive response to physostigmine was significantly greater in BPD patients, but not other personality disorder patients, compared to normal controls (p < 0.05). There was a correlation between the peak placebo-corrected depressive response to physostigmine and a group of BPD traits related to affective instability but not a group of BPD traits related to impulsivity. There was no correlation in any group between mood response to physostigmine and changes in plasma cortisol, prolactin, or growth hormone, or to nausea or other side effects following physostigmine infusion. These data suggest that there is an association between BPD and acute depressive responses to physostigmine challenge, and that the cholinergic system may be involved in the regulation of affect in Axis II disorders.

Adult↗

The effect of Tn916 insertions on contour-clamped homogeneous electrophoresis patterns of Enterococcus faecalis.

Contour-clamped homogeneous gel electrophoresis has increasingly been used and has generally been considered the method of choice for the delineation of enterococcial strains. It has been suggested that the contour-clamped homogeneous electric field (CHEF) electrophoresis digestion patterns of genomic DNA indicate the relatedness of strains when SmaI patterns differ by six or fewer bands. To evaluate the potential reasons for the diversity of bands among clonally related isolates, we studied plasmid-free Enterococcus faecalis FA2-2 and derivatives with transposon Tn916 (encoding for tetracycline resistance) insertions on the chromosome. We obtained derivatives with seven different Tn916 insertion sites and up to two copies of Tn916 on the chromosome, resulting in differences of one to seven bands by CHEF electrophoresis; eight different patterns were observed. With Tn916 insertions, there was either (i) loss of a band(s) with the generation of a new band(s), (ii) the generation of a new band(s) only, or (iii) the loss of a band(s) with no new visible band(s). These results indicate that strains can have up to seven different SmaI bands by CHEF electrophoresis and still be closely related.

Bacterial Typing Techniques↗

Assessing axis II disorders by informant interview.

Although much of personality disorder research depends on diagnostic data obtained directly from patients, this approach has rarely been compared to interviews with knowledgeable informants. The purpose of this study was to determine the diagnostic agreement between these two assessment methods, as well as their relative contribution to the formulation of consensus diagnoses. Sixty-two psychiatric patients were assessed directly with the Structured Interview for DSM-III Personality Disorders (SIDP), and were asked to nominate an informant--either a family member or friend--to provide information about the patient in an interview with the same instrument. Informant interviews were conducted blind to patient-based information whenever feasible, and diagnostic consensus was achieved by an independent review of all available data by a senior clinician. Diagnostic agreement between patient-based and informant-based personality disorder interview was poor, confirming the findings of two previous studies. Information obtained from patients tended to be given greater weight in formulating consensus diagnoses than information provided by informants. However, about one quarter of diagnostic disagreements were resolved in favor of informant-based information. In contrast to a previous study, the inclusion of informant information did not appear to reveal greater psychopathology in patients. We conclude that supplementing direct patient interview with data provided by a knowledgeable informant appears to enhance the resolution of some personality disorder diagnoses. The utility of informant interviews may depend on an analysis of the costs and benefits of this additional degree of descriptive refinement.

Adult↗

Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin.

Acidic conditions within the endosomal lumen induce the T domain of receptor-bound diphtheria toxin (DT) to insert into the endosomal membrane and mediate translocation of the toxin's catalytic domain to the cytosol. A conformational rearrangement in the toxin occurring near pH5 allows a buried apolar helical hairpin of the native T domain (helices TH8 and TH9) to undergo membrane insertion. If the inserted hairpin spans the bilayer, as hypothesized, then the two acidic residues within the TL5 interhelical loop, Glu 349 and Asp 352, should become exposed at the neutral cytosolic face of the membrane and reionize. To investigate the roles of these residues in toxin action, we characterized mutant toxins in which one or both acidic residues had been replaced with nonionizable ones. Each of two double mutants examined showed a several-fold reduction in cytotoxicity in 24-h Vero cell assays (sixfold for E349A + D352A and fourfold for E349Q + D352N), whereas the individual E349Q and D352N mutations caused smaller reductions in toxicity. The single and double mutations also attenuated the toxin's ability to permeabilize Vero cells to Rb+ at low pH and decreased channel formation by the toxin in artificial planar bilayers. Neither of the double mutations affected the pH-dependence profile of the toxin's conformational rearrangement in solution, as measured by binding of the hydrophobic fluorophore, 2-p-toluidinyl-naphthalene 6-sulfonate. The results demonstrate that, although there is no absolute requirement for an acidic residue within the TL5 loop for toxicity, Glu 349 and Asp 352 do significantly enhance the biological activity of the protein. The data are consistent with a model in which ionization of these residues at the cytosolic face of the endosomal membrane stabilizes the TH8/TH9 hairpin in a transmembrane configuration, thereby facilitating channel formation and translocation of the toxin's catalytic chain.

Animals↗

D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder.

The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine-associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge.

Adult↗

The factor structure of schizotypal symptoms in a clinical population.

There is some support for the hypothesis that the factor structure of schizophrenia symptoms is similar to the factor structure of schizotypal symptoms in nonschizophrenia populations. However, no studies to date have examined schizotypal symptoms in patients with personality disorders. In this study, confirmatory factor analyses were conducted to test the relative fit of several models of the factorial structure of schizotypal symptoms in patients diagnosed with personality disorders. The EQS: Structural Equations Program was used to analyze DSM-III symptoms of schizotypal personality disorder (SPD) based on structured clinical interviews with 213 patients meeting a diagnosis for at least one personality disorder. A subgroup of the total sample was also evaluated for DSM-III-R criteria (n = 143) to test competing models of the DSM-III-R symptoms of SPD. A three-factor model consisting of a cognitive-perceptual, interpersonal, and paranoid factor yielded the best fit to the data relative to the other models tested. These results suggest that the three-factor model of schizophrenia symptoms may not entirely correspond to the factors underlying milder schizotypal symptoms expressed in a clinical population. It is suggested that future research focus on both the similarities and the differences between SPD and schizophrenia.

Adult↗

Cognitive function and biological correlates of cognitive performance in schizotypal personality disorder.

There is evidence that some schizophrenic patients have deficits on tests of cognitive function, particularly tests of executive function, including the Wisconsin Card Sorting Test (WCST) and the Trail-making Test, Part B. This study was conducted to determine the generalizability of these findings across the schizophrenia spectrum to schizotypal personality disorder (SPD). Forty DSM-III SPD patients, 56 nonschizophrenia-related other personality disorder (OPD) patients, and 32 normal volunteers from two medical centers performed tests of executive function such as the WCST, Trail-making Part B, Stroop Word-Color Test, and Verbal Fluency, as well as tests of more general intellectual functioning such as the Wechsler Intelligence Scale-Revised Vocabulary and Block Design subtests, and Trail-making Part A. SPD patients performed more poorly on the WCST and on Trail-making Part B than did OPD patients or normal subjects; the groups did not differ on tests of general intellectual functioning. SPD patients may share some of the cognitive deficits observed in schizophrenia.

Adult↗

Lateral ventricular enlargement in schizotypal personality disorder.

Although an increase in the ratio of ventricular space to brain (ventricle-brain ratio), VBR) on computed tomography (CT) has been among the most robust findings in chronic schizophrenia, VBR has not been investigated in a large, well-characterized clinical population of patients with schizotypal personality disorder (SPD), a clinical entity with a phenomenologic, gentle biological, and treatment response relationship to chronic schizophrenia. Accordingly, CT scans were obtained in 36 male SPD patients, 23 males with other personality disorders, 133 male schizophrenic patients, and 42 male normal volunteers. The mean body of the lateral VBR was significantly greater in the SPD patients than in the patients with other personality disorders. The VBR of the SPD patients did not differ significantly from either that of the normal volunteers or the schizophrenic patients but was intermediate between the two groups. There were no correlations with either psychotic-like or deficit-related symptoms of SPD in either the SPD or total personality disorder cohorts. SPD patients, like schizophrenic patients, may have increased VBRs compared wit patients with other personality disorders; their VBRs fall between the means of schizophrenic patients and normal control subjects.

Adult↗

Cytogenetic and flow cytometric analysis of a pancreatoblastoma.

A pancreatoblastoma from a 4-year old male was examined by flow cytometric ploidy analysis and cytogenetics. To detect differences within the tumor, the specimen was divided into four portions and sampled separately. Flow analysis revealed that each sample contained a diploid and a tetraploid population of tumor cells. These findings correlated well with the cytogenetic analysis, which also revealed differences in structural rearrangements between samples. A t(13;22)(q10;q10) was the only rearrangement found in near-diploid cells as well as one near-tetraploid line. Other common structural changes in near-tetraploid cells included t(13;13)(q10;q10), i(6p)(p10), and del(1). Chromosomes 1, 6, 13, and 22 were consistently missing from all near-tetraploid cells lines. To our knowledge, this is the first flow cytometric and cytogenetic study of a pancreatoblastoma.

Child, Preschool↗

Characterization of antimicrobial resistance in enterococci of animal origin.

Among 97 enterococci cultured from animals, gentamicin MICs were > or = 2,000 micrograms/ml for 9 isolates and between 250 and 1,024 micrograms/ml for 6 isolates. For two isolates tested (gentamicin MICs, 256 and 512 micrograms/ml, respectively), there was no in vitro synergy with penicillin plus gentamicin, resistance was transferable, and there was no hybridization with a probe specific for 6'-aminoglycoside acetyltransferase-2"-aminoglycoside phosphotransferase. The results of the study indicate the presence of a unique gentamicin resistance genotype in enterococci of animal origin.

Animals↗

Medical disorders in the schizophrenic patient.

OBJECTIVE: The primary purpose of this review of medical disorders in the schizophrenic patient is to provide the clinician interested in Consultation/Liaison psychiatry and psychosomatic issues a comprehensive and current review of the subject. METHOD: The authors used the Index Medicus and Medline to find recent review articles and research articles related to medical disorders in the schizophrenic patient. Also, the authors described their clinical experience in Consultation/Liaison psychiatry working with schizophrenic patients in a large, tertiary-care academic medical center. RESULTS: The authors divided their review into: 1) mortality and morbidity in schizophrenia, 2) differential diagnosis, 3) specific comorbidity management problems, 4) caring for schizophrenics on medical/surgical wards, and 5) antipsychotic drugs in the medical setting. Schizophrenia remains an important subject for Consultation/Liaison psychiatrists. CONCLUSIONS: Schizophrenia and its protean manifestations confound the care of the medical patient. The psychosis of schizophrenia may impair the patient's capacity to recognize or articulate emerging medical illness, or to respond to therapeutic interventions. The psychiatrist caring for and consulting on patients with medical illnesses bears major responsibility for understanding the complex interface of schizophrenia and medical illnesses. Psychiatrists need to educate our medical and surgical colleagues how schizophrenia alters the usual presentation, clinical course, and response to treatment of common medical and surgical illnesses.

Antipsychotic Agents↗