Search PubMed⌕ Search

Biomedical subjects

R E Hoffman

Publications and source records attributed to R E Hoffman.

At least 19 recordsLinked to original sources

Lithium reduction of the bowl-shaped C60 fragment diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene: an interplay between experiment and calculation.

Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene (DIC) (one of the smallest symmetrical bowl-shaped fragments of C60) and its tetra-tert-butyl derivative are reduced with lithium metal to yield dianions and tetraanions. Due to the high degree of symmetry (C2v) of DIC and its derivative, their NMR spectra cannot be assigned using the standard two-dimensional NMR techniques. A novel carbon-edited NOESY method was used to complete the assignments of the neutral and dianion species, whereas the tetraanions are aided by DFT calculations for their assignment. Experimental charge-distribution patterns were obtained and match those of the calculations. An extension of the empirical approach for estimating the charge distribution from the 13C NMR spectra enables a direct comparison between experimentally derived charge-distribution data and the computed electron density in each of the lowest unoccupied molecular orbitals. The overall picture evolving from the orbital structure of DIC is presented and reflects the surface reactivity of C60.

Journal Article↗

Serratia liquefaciens bloodstream infections from contamination of epoetin alfa at a hemodialysis center.

BACKGROUND: In a one month period, 10 Serratia liquefaciens bloodstream infections and 6 pyrogenic reactions occurred in outpatients at a hemodialysis center. METHODS: We performed a cohort study of all hemodialysis sessions on days that staff members reported S. liquefaciens bloodstream infections or pyrogenic reactions. We reviewed procedures and cultured samples of water, medications, soaps, and hand lotions and swabs from the hands of personnel. RESULTS: We analyzed 208 sessions involving 48 patients. In 12 sessions, patients had S. liquefaciens bloodstream infections, and in 8, patients had pyrogenic reactions without bloodstream infection. Sessions with infections or reactions were associated with higher median doses of epoetin alfa than the 188 other sessions (6500 vs. 4000 U, P=0.03) and were more common during afternoon or evening shifts than morning shifts (P=0.03). Sessions with infections or reactions were associated with doses of epoetin alfa of more than 4000 U (multivariate odds ratio, 4.0; 95 percent confidence interval, 1.3 to 12.3). A review of procedures revealed that preservative-free, single-use vials of epoetin alfa were punctured multiple times, and residual epoetin alfa from multiple vials was pooled and administered to patients. S. liquefaciens was isolated from pooled epoetin alfa, empty vials of epoetin alfa that had been pooled, antibacterial soap, and hand lotion. All the isolates were identical by pulsed-field gel electrophoresis. After the practice of pooling epoetin alfa was discontinued and the contaminated soap and lotion were replaced, no further S. liquefaciens bloodstream infections or pyrogenic reactions occurred at this hemodialysis facility. CONCLUSIONS: Puncturing single-use vials multiple times and pooling preservative-free epoetin alfa caused this outbreak of bloodstream infections in a hemodialysis unit. To prevent similar outbreaks, medical personnel should follow the manufacturer's guidelines for the use of preservative-free medications.

Adult↗

Public health response to 2 clinical cases of blastomycosis in colorado residents.

We summarize the public health response after the identification of 2 cases of pneumonia caused by Blastomyces dermatitidis infection in Colorado residents. The response to these cases emphasizes the need for physicians to add fungal infection to the list of differential diagnoses for patients who have refractory pneumonia, even those who live in areas of nonendemicity.

Adult↗

Creutzfeldt-Jakob disease after receipt of a previously unimplicated brand of dura mater graft.

BACKGROUND: Iatrogenic Creutzfeldt-Jakob disease (CJD) transmission via dura mater grafts has been reported in many countries. In September 1998, a 39-year-old Colorado woman was reported as having suspected CJD after receiving a dura mater graft 6 years earlier. METHODS: An investigation was initiated to confirm the diagnosis of CJD and assess the possible source of CJD transmission. The authors determined the presence or absence of other known CJD risk factors, checked for epidemiologic evidence of possible CJD transmission via neurosurgical instruments, and evaluated the procedures used in the collection and processing of the graft, including whether the donor may have had CJD. RESULTS: The CJD diagnosis was confirmed in the dural graft recipient by neuropathologic and immunodiagnostic evaluation of the autopsy brain tissue. She had no history of receipt of cadaveric pituitary hormones or corneal grafts or of CJD in her family. The authors found no patients who underwent a neurosurgical procedure within 6 months before or 5 months after the patient's surgery in 1992 who had been diagnosed with CJD. The dura mater was obtained from a 57-year-old man with a history of dysarthria, ataxia, and behavioral changes of uncertain origin. The graft was commercially prepared by use of a process that included treatment with 0.1 N sodium hydroxide and avoided commingling of dura from different donors. CONCLUSIONS: The patient's age, absence of evidence for other sources of CJD, the latent period, and the report of an unexplained neurologic illness in the donor of the dura mater indicate that the graft was the most likely source of CJD in this patient.

Adult↗

Cortical instability and the mechanism of mania: a neural network simulation and perceptual test.

BACKGROUND: A previous neural network simulation suggested that manic states arise from excessive levels of noise that destabilize neural representations. The Necker cube stick figure provides a simple perceptual task that assesses stability of gestalt-type representations. METHODS: A neural network was developed that included a simulation of the Necker cube task. Noise was added to induce maniclike jumps from one representation to another. A parallel study of Necker cube perception was conducted with 16 patients diagnosed with manic-spectrum disorder, 18 patients with schizophrenia, and 19 normal control subjects. Cognitive speed and rate of indiscriminate responses were assessed using an auditory continuous performance task. RESULTS: During processing of the "Necker cube" stimulus, the reversal rate of the noise-destabilized "manic" network was increased by 30%. In the human subject study, the median score of Necker cube reversal rates for manic-spectrum patients was roughly twice that of normal control subjects and patients with schizophrenia. Accelerated reversal rates in the manic-spectrum group were not attributable to excessive cognitive speed or higher rates of indiscriminate responses. CONCLUSIONS: The two studies, considered together, support the hypothesis that excessive cortical noise destabilizes neural representations in manic-spectrum patients.

Adult↗

Anatomic basis of sequence-dependent predictability exhibited by nigral dopamine neuron firing patterns.

Interspike intervals (ISIs) of dopamine (DA) neurons recorded in the substantia nigra are predicted partially by their immediate prior history. This study was designed to assess neuroanatomic origins of these sequential relationships. ISI data recorded from three groups of nigral DA neurons were studied: 1) 16 neurons recorded in unlesioned animals, 2) 14 neurons recorded after forebrain hemisection, 3) 12 neurons recorded after partial forebrain hemisection that reproduced nonspecific effects of the surgical lesion while leaving forebrain connections intact. As predicted, DA neurons recorded after full forebrain hemisection yielded statistically significant reductions in sequential predictability relative to control neurons and neurons recorded following partial hemisection. These data support the hypothesis that the sequence-dependent behavior of DA neurons arise in part from interactions with forebrain structures. ISI sequences recorded from unlesioned rats demonstrated maximum predictability when an average of 3.7 prior events were incorporated into the forecasting algorithm, thereby suggesting a physiological process whose "depth" of history-dependence is approximately 600-800 msec. Additional studies examining the functional significance of sequence-dependent ISI structure exhibited by nigral DA neurons are indicated.

Action Potentials↗

EEG monitoring in depressed patients undergoing repetitive transcranial magnetic stimulation.

To date, 33 subjects diagnosed with major depressive disorder have undergone transcranial magnetic stimulation (TMS) in the authors' clinic. Five of these patients showed minimal electroencephalogram (EEG) variants at baseline. The authors describe the course of treatment and serial EEGs in 3 of the 5 patients who did not show progressive EEG changes in association with active rTMS. These three cases suggest that minimal EEG anomalies at baseline need not serve as a contraindication to undergoing rTMS. Two patients with progressive EEG changes in association with sham rTMS in one and active rTMS in the other are also discussed.

Adult↗

Neural network models of schizophrenia.

There is considerable neurobiological evidence suggesting that schizophrenia is associated with reduced corticocortical connectivity. The authors describe two neural network computer simulations that explore functional consequences of these abnormalities. The first utilized an "attractor" neural network capable of content-addressable memory. Application of a pruning rule that eliminated weaker connections over longer distances produced functional fragmentation and the emergence of localized, "parasitic" attractors that intruded into network dynamics. These pathologies generally were expressed only when input information was ambiguous and provide models for delusions and cognitive disorganization. A second neural network simulation examined effects of corticocortical pruning in a speech perception network. Excessive pruning caused the network to produce percepts spontaneously, that is, in the absence of inputs, thereby simulating hallucinations. The "hallucinating" network also demonstrated subtle impairments in narrative speech perception. A parallel study of human patients found similar impairments when comparing hallucinating patients with nonhallucinating patients. In addition, the authors have used transcranial magnetic stimulation (TMS) to directly probe speech perception neurocircuitry in patients with these hallucinations. As predicted by the neural network model, the authors confirmed that "suppressive" low-frequency TMS reduces auditory hallucinations. Neural network simulations provide empirically testable concepts linking phenomenological, cognitive, and neurobiological findings in schizophrenia.

Brain↗

Individual and community risks of measles and pertussis associated with personal exemptions to immunization.

CONTEXT: The risk of vaccine-preventable diseases among children who have philosophical and religious exemptions from immunization has been understudied. OBJECTIVES: To evaluate whether personal exemption from immunization is associated with risk of measles and pertussis at individual and community levels. DESIGN, SETTING, AND PARTICIPANTS: Population-based, retrospective cohort study using data collected on standardized forms regarding all reported measles and pertussis cases among children aged 3 to 18 years in Colorado during 1987-1998. MAIN OUTCOME MEASURES: Relative risk of measles and pertussis among exemptors and vaccinated children; association between incidence rates among vaccinated children and frequency of exemptors in Colorado counties; association between school outbreaks and frequency of exemptors in schools; and risk associated with exposure to an exemptor in measles outbreaks. RESULTS: Exemptors were 22.2 times (95% confidence interval [CI], 15.9-31.1) more likely to acquire measles and 5.9 times (95% CI, 4.2-8.2) more likely to acquire pertussis than vaccinated children. After adjusting for confounders, the frequency of exemptors in a county was associated with the incidence rate of measles (relative risk [RR], 1.6; 95% CI, 1.0-2.4) and pertussis (RR, 1.9; 95% CI, 1.7-2.1) in vaccinated children. Schools with pertussis outbreaks had more exemptors (mean, 4.3% of students) than schools without outbreaks (1. 5% of students; P =.001). At least 11% of vaccinated children in measles outbreaks acquired infection through contact with an exemptor. CONCLUSIONS: The risk of measles and pertussis is elevated in personal exemptors. Public health personnel should recognize the potential effect of exemptors in outbreaks in their communities, and parents should be made aware of the risks involved in not vaccinating their children.

Adolescent↗

A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression.

BACKGROUND: Multiple groups have reported on the use of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant major depression. The purpose of this study is to assess the efficacy of rTMS in unmedicated, treatment-resistant patients who meet criteria for major depression. METHODS: Depressed subjects, who had failed to respond to a median of four treatment trials, were assigned in a randomized double-blind manner to receive either active (n = 10; 20 2-sec trains of 20 Hz stimulation with 58-sec intervals; delivered at 80% motor threshold with the figure-of-eight coil positioned over the left dorsolateral prefrontal cortex) or sham (n = 10; similar conditions with the coil elevated and angled 45 degrees tangentially to the scalp) rTMS. These sequences were applied during 10 consecutive weekdays. Continuous electroencephalogram sampling and daily motor threshold determinations were also obtained. RESULTS: The group mean 25-item Hamilton Depression Rating Scale (HDRS) score was 37.2 (+/- 2.0 SEM) points. Adjusted mean decreases in HDRS scores were 14.0 (+/- 3.7) and 0.2 (+/- 4.1) points for the active and control groups, respectively (p <.05). One of 10 subjects receiving active treatment demonstrated a robust response (i.e., HDRS decreased from 47 to 7 points); three other patients demonstrated 40-45% decreases in HDRS scores. No patients receiving sham treatment demonstrated partial or full responses. CONCLUSIONS: A 2-week course of active rTMS resulted in statistically significant but clinically modest reductions of depressive symptoms, as compared to sham rTMS in a population characterized by treatment resistance.

Adolescent↗

Schizophrenia as a disorder of developmentally reduced synaptic connectivity.

Recent postmortem and neuroimaging studies of schizophrenia delineate changes in brain structure and volume that appear to arise from a reduction of neuritic processes (such as dendrites and synapses) rather than loss of neuronal or glial cell bodies. To account for these findings, we propose a pathophysiological model of reduced synaptic connectivity arising from disturbances of brain development active during perinatal and adolescent periods. We review a computer simulation of the elimination of the synaptic connections that models normal cognitive development and psychotic symptom formation. We describe the model's key parameters and discuss how they can account for important aspects of schizophrenia, including its unique symptoms, short- and long-term course, typical age of onset, neurodevelopmental deficits, limited neurodegenerative progression, sex differences, and more. We discuss some of the model's predictions and questions raised for basic research, early detection, and preventive intervention.

Adolescent↗

Adolescent suicide and household access to firearms in Colorado: results of a case-control study.

PURPOSE: To determine whether, compared with age- and sex-matched controls who did not commit suicide, adolescents who committed suicide by firearms were more likely to have had household access to firearms (after adjusting for significant risk factors for adolescent suicide). METHODS: A case-control study design was used; case subjects were Colorado adolescents who committed suicide between 1991 and 1993; controls were sex- and age-matched adolescents who were randomly selected from the same school the subjects had attended. Interviews were conducted with the parent or guardian of cases and controls. RESULTS: Of the 36 case subjects in this study, 67% committed suicide using a gun obtained from their home. Adolescent suicide victims who committed suicide by firearms were significantly more likely to have a firearm in their home (72%) than age- and sex-matched community controls (50%), after adjusting for significant risk factors. Conduct disorder and previous mental health treatment were also found to be independent risk factors for adolescent firearm suicide. CONCLUSIONS: Two types of public health interventions to prevent adolescent firearm suicides are likely to be successful: (a) limiting household access to firearms, and (b) identifying adolescents at high risk of firearm suicide.

Adolescent↗

Transcranial magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated "voices".

BACKGROUND: Prior studies suggest that auditory hallucinations of "voices" arise from activation of speech perception areas of the cerebral cortex. Low frequency transcranial magnetic stimulation (TMS) can reduce cortical activation. METHODS: We have studied three schizophrenic patients reporting persistent auditory hallucinations to determine if low frequency TMS could curtail these experiences. One hertz stimulation of left temporoparietal cortex was compared with sham stimulation using a double-blind, cross-over design. RESULTS: All three patients demonstrated greater improvement in hallucination severity following active stimulation compared to sham stimulation. Two of the three patients reported near total cessation of hallucinations for > or = 2 weeks. CONCLUSIONS: TMS may advance our understanding of the mechanism and treatment of auditory hallucinations.

Adult↗

Increased protections during a measles outbreak of children previously vaccinated with a second dose of measles-mumps-rubella vaccine.

BACKGROUND: In 1989 a second dose of measles vaccine was recommended for US children to prevent school outbreaks of measles. Coverage of school age children with a second dose remains incomplete, and data on the effectiveness of this recommendation are limited. We investigated a measles outbreak in Mesa County, CO, in December, 1994, and evaluated the efficacy of preoutbreak immunizations at an elementary school (School A) where many students had received two doses. METHODS: All reported suspected cases of measles were investigated; cases that met a clinical case definition were tested by a measles IgM antibody assay. A confirmed case required laboratory confirmation or had to meet the clinical case definition and be epidemiologically linked to a confirmed case. Vaccination records of students at School A were reviewed. The effectiveness of one and two doses of measles vaccine was estimated using logistic regression. RESULTS: Sixty-two confirmed cases were reported, including 17 at School A. At School A the attack rate in unvaccinated children (7 of 16, 44%) was higher than in those with 1 dose (10 of 320, 3%) or 2 doses (0 of 289, 0%). Estimated vaccine effectiveness was 92% for 1 dose and 100% for 2 doses. Two doses were better than one dose in decreasing the likelihood of acquiring measles (P = 0.003). CONCLUSIONS: The lower attack rate among two dose recipients provides evidence that a two dose strategy can help prevent measles in schools. Administering the second dose at elementary school entry can help prevent the persistence of susceptible cohorts of children and is likely to be important in sustaining elimination of indigenous transmission of measles in the United States.

Adolescent↗

New methods for studying hallucinated 'voices' in schizophrenia.

The mechanism of hallucinated speech or 'voices', a symptom commonly reported by schizophrenic patients, is poorly understood. We have undertaken two types of study to explore the hypothesis that this symptom arises from pathologically altered speech perception networks. The first consists of neural network computer simulations of narrative speech perception. We have shown that if these networks are partially disconnected or undergo a 'monamine' neuromodulatory disturbance, 'hallucinated speech' (speech percepts occurring in the absence of phonetic input) are simulated as well as specific speech perception impairments. The latter finding prompted us to conduct parallel studies of actual schizophrenic patients using a 'masked speech tracking' (MST) task. MST requires subjects to track narrative speech the phonetic clarity of which is reduced with superimposed multispeaker 'babble.' Hallucinators demonstrated speech perception impairments and experimentally induced perceptual 'illusions' which clearly differentiated them from non-hallucinators and normal controls. Our results support the hypothesis that 'voices' are spurious products of altered speech perception networks.

Adolescent↗

Selective speech perception alterations in schizophrenic patients reporting hallucinated "voices".

OBJECTIVE: The authors tested a model of hallucinated "voices" based on a neural network computer simulation of disordered speech perception. METHOD: Twenty-four patients with schizophrenia spectrum disorders who reported hallucinated voices were compared with 21 patients with schizophrenia spectrum disorders who did not report voices and 26 normal subjects. Narrative speech perception was assessed through use of a masked speech tracking task with three levels of superimposed phonetic noise. A sentence repetition task was used to assess grammar-dependent verbal working memory, and an auditory continuous performance task was used to assess nonlanguage attention. RESULTS: Masked speech tracking task and sentence repetition performance by hallucinating patients was impaired relative to both nonhallucinating patients and normal subjects. Although both hallucinating and nonhallucinating patients demonstrated auditory attention impairments when compared to normal subjects, the two patient groups did not differ with respect to these variables. CONCLUSIONS: Results support the hypothesis that hallucinated voices in schizophrenia arise from disrupted speech perception and verbal working memory systems rather than from nonlanguage cognitive or attentional deficits.

Adult↗