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Biomedical subjects

Richard Goldstein

Publications and source records attributed to Richard Goldstein.

At least 19 recordsLinked to original sources
PubMed2006

Diversity and antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae carriage isolates in the post-heptavalent conjugate vaccine era.

BACKGROUND: In response to the selective pressure of pneumococcal conjugate vaccine, increased asymptomatic carriage of antibiotic-nonsusceptible nonvaccine serotypes (NVTs) has been observed. Possible mechanisms include de novo acquisition of resistance, serotype switching, introduction of new clones, and expansion of existing clones. METHODS: To investigate the process of increased antibiotic nonsusceptibility among replacing serotypes, we applied multilocus sequence typing to samples of 126 and 222 pneumococci collected in 2001 and 2004, respectively, from the nasopharynges of children <7 years of age in 16 Massachusetts communities. RESULTS: We found no evidence of penicillin resistance due to either serotype switching or de novo acquisition. Nonetheless, resistance increased through the expansion of previously recognized clones of NVTs, particularly in serotypes 19A, 15A, and 35B. In 19A, several unrelated clones increased in frequency, whereas, in the other 2 serotypes, single resistant lineages were responsible for the increased prevalence of resistant strains. CONCLUSIONS: The decreased prevalence of antibiotic resistance with the introduction of heptavalent pneumococcal conjugate vaccine is likely to be partially eroded over time as vaccine-included serotypes are replaced by resistant clones of NVTs. The clinical significance of this will depend on the pathogenic potential of replacing clones to cause local (e.g., otitis media) or invasive disease.

Anti-Bacterial Agents↗
PubMed2006

Role of complement in defense of the middle ear revealed by restoring the virulence of nontypeable Haemophilus influenzae siaB mutants.

Nontypeable (NT) Haemophilus influenzae is an important cause of otitis media in children. We have shown previously that NT H. influenzae mutants defective in their ability to sialylate lipopolysaccharide (LPS), called siaB mutants, show attenuated virulence in a chinchilla model of experimental otitis media (EOM). We show that complement is a key arm of host innate immunity against NT H. influenzae-induced EOM. Depleting complement in chinchillas by use of cobra venom factor (CoVF) rendered two otherwise avirulent siaB mutants fully virulent and able to cause EOM with severity similar to that of wild-type strains. Clearance of infection caused by siaB mutants in CoVF-treated animals coincided with reappearance of C3. Wild-type strains were more resistant to direct complement-mediated killing than their siaB mutants. The serum-resistant strain bound less C3 and C4 than the serum-sensitive strain. Neither NT H. influenzae strain tested bound factor H (alternative complement pathway regulator). Selective activation of the alternative pathway resulted in more C3 binding to siaB mutants. LPS sialylation had a more profound impact on the amount of alternative-pathway-mediated C3 binding ( approximately 5-fold decrease in fluorescence) when LPS was the main C3 target, as occurred on the more serum-resistant strain. In contrast, only an approximately 1.5-fold decrease in fluorescence intensity of C3 binding was seen with the serum-sensitive strain, where surface proteins predominantly bound C3. Differences in binding sites for C3 and C4 may account for variations in serum resistance between NT H. influenzae strains, which in turn may impact their virulence. These data demonstrate a central role for complement in innate immune defenses against NT H. influenzae infections and specifically EOM.

Animals↗
PubMed2006

Excessive daytime sleepiness in patients with Parkinson's disease: a polysomnography study.

To investigate excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD), the reasons for which have not yet been clarified, polysomnography (PSG) and the Multiple Sleep Latency Test (MSLT) were performed in 46 patients with PD, and, in addition, PSG was performed in 30 healthy controls. Assessment included Epworth Sleepiness Score (ESS), Mini-Mental State Examination (MMSE), and Hamilton Test (HT) for depression. Fifty percent of PD patients reported EDS (ESS, 10 +/- 4.5 vs. 6.9 +/- 3.7; P = 0.01). Compared with controls, PD patients as a group had lower sleep efficiency (65 +/- 22 vs. 77 +/- 14; P = 0.03), a longer Stage 2 (73 +/- 12 vs. 67 +/- 12; P = 0.03), and a shorter rapid eye movement stage (8 +/- 8 vs. 17 +/- 8; P < 0.001). Clinical data and sleep characteristics were similar in PD with/without EDS. Of interest, patients treated with clonazepam (CLNZ) had lower EDS than those without CLNZ (ESS, 7.9 +/- 4.7 vs. 11.3 +/- 4.0; P = 0.03). These patients suffered less periodic leg movement during sleep (2.1 +/- 2.7 vs. 12.4 +/- 28; P = 0.04), which might explain the finding. No correlation was found between ESS, MSLT, and all other clinical features analyzed. In PD patients, according to the data obtained, severity of EDS does not depend on any specific clinical factor and the etiology is probably multifactorial. Paradoxically, PD patients treated with CLNZ were less sleepy than patients not treated with CLNZ.

Aged↗
PubMed2006

Near-infrared spectroscopy and imaging for investigating stroke rehabilitation: test-retest reliability and review of the literature.

OBJECTIVES: To review the use of near-infrared spectroscopy (NIRS) in stroke rehabilitation and to evaluate NIRS test-retest reliability within-session on a motor control task commonly used in neuroimaging of stroke recovery. DESIGN: Cohort study. SETTING: Hospital-based research laboratory. PARTICIPANTS: Nineteen healthy control subjects (age range, 22-55y). INTERVENTIONS: Subjects performed 2 experimental runs of a finger-opposition task in a block-design paradigm (finger opposition alternated with a fixation rest period) while undergoing multichannel NIRS and physiologic monitoring. MAIN OUTCOME MEASURE: Reliability coefficients (Pearson r) for oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb) correlated amplitude modulations across measurement channels during individual blocks and block averages. RESULTS: Correlations between single blocks (ie, 16-s slices of data) exhibited a correlation intercept of .33+/-.09 for O(2)Hb. This value was minimally decreased by increasing lag between compared blocks (slope, -.012; P=.019) but was substantially enhanced by averaging across blocks (within-run slope, .11; between-run slope, .044). Correlations using 64 seconds of data reached 0.6. Results for HHb were virtually identical. CONCLUSIONS: NIRS modulations were repeatable even when comparing very short segments of data. When averaging longer data segments, the test-retest correspondences compared favorably to neuroimaging using other modalities. This suggests that NIRS is a reliable tool for longitudinal stroke rehabilitation and recovery studies.

Adult↗
PubMed2006

Validity and reliability of the Community Integration Program Questionnaire.

The Community Integration Program Questionnaire was developed to measure various quantifiable characteristics of community integration programs for people with brain injury. There are three versions: one for outpatient facility-based, one for residential and one for home programs. In this study questionnaires were administered to directors and associate directors of seven programs. A research assistant then went on-site to collect corresponding data using patient records, planning books and schedules, annual and quarterly reports, employee lists, staff curricula vitae, census data, insurance payment data, team meeting notes, incident reports, and staff logs. Matching criteria between questionnaire and on-site data were established before either was collected. The survey data matched data acquired on-site in 42.2, 56.4, and 56.8% of questions in the three versions, respectively. Interviewers and a second listener recorded the same information 91.5% of the time across seven program interviews. For two programs, comparisons between a Program Director and Program Coordinator yielded matches on 42.8 and 40.6% of questions, respectively. In conclusion, the Community Integration Program Questionnaire does not have acceptable construct validity and inter-rater reliability. Researchers requiring information about quantifiable characteristics of community integration programs should go on-site to collect the data.

Brain Injuries↗
PubMed2006

Hypocalcemia after neck exploration for untreated primary hyperparathyroidism.

Hypocalcemia after neck exploration for hyperparathyroidism is an important postoperative management issue. With increasing acceptance of less invasive surgical approaches, hypocalcemia is less frequent. This study was conducted to evaluate postoperative hypocalcemia after current surgical exploration techniques in patients with untreated primary hyperparathyroidism. From the University of Louisville parathyroid database, charts of patients undergoing surgery for untreated primary hyperparathyroidism from May 1, 1998 to May 30, 2004 were reviewed. Data was analyzed based on age, sex, preoperative calcium and parathyroid hormone levels, preexisting diseases, and extent of neck exploration. One hundred sixty-nine patients were identified with adequate data for analysis. Transient postoperative hypocalcemia occurred in 21 per cent (36/169) for the total group, in 18 per cent (22/125) after minimally invasive radio-guided parathyroidectomy, and in 32 per cent (14/44) after bilateral neck exploration. Patients with postoperative hypocalcemia had a statistically significant association with older age and pre-existing hypertension. Patients with postoperative hypocalcemia were more likely to have undergone longer surgical procedures and were more likely to have had pre-existing diabetes and mental disorders. These findings were not statistically significant and were considered trends. The frequency of osteoporosis in the hypocalcemia group was increased but was not significant. Transient hypocalcemia occurred in 21 per cent of patients after parathyroid surgery. It was more likely after bilateral neck exploration, a longer duration of surgery, and with hypertension, diabetes, and mental disorders.

Age Factors↗
PubMed2005

Characteristics of home-based community integration programmes for adults with brain injury.

OBJECTIVES: To conduct a nationwide telephone survey in order to gather data on some of the quantifiable characteristics of home-based community integration programmes available in the US to adults with brain injury. DESIGN: Survey. METHODS: The Community Integration Programme Questionnaire (CIPQ) was used to interview 13 home-based community integration programmes. This study then used descriptive statistics to analyse the characteristics of the programmes. OUTCOME: There was a good deal of variability in client and programmatic characteristics. CONCLUSIONS: There is considerable variability in characteristics among home-based community integration programmes.

Adult↗
PubMed2005

Predictors of survival after severe dysphagic stroke.

BACKGROUND AND PURPOSE: Dysphagia is estimated to occur in up to 50% of the stroke neurorehabilitation population. Those patients with severe neurogenic oropharyngeal dysphagia (NOD) may receive feeding gastrostomy tubes (FGT) if noninvasive therapies prove ineffective in eliminating aspiration or sustaining adequate nutritional intake. Our aim was to quantify the recovery of swallowing function, and to identify variables predictive of survival after dysphagic stroke requiring FGT placement. METHODS: We identified consecutive stroke patients with severe dysphagic stroke requiring FGT placement admitted to a rehabilitation hospital between May 1998 and October 2001. The medical records were reviewed, and demographic, clinical, videofluoroscopic (VSS) and neuroimaging information were abstracted. A follow-up telephone interview was performed to determine whether the FGT was still in use, had been removed,or if the patient had died. State death certificate records were reviewed to ascertain date of death for subjects who had expired by the time of follow-up. Univariate and multivariate analyses were performed. RESULTS: 11.6 % (77/664) of stroke patients admitted during the study period had severe dysphagic stroke with FGT insertion. Follow-up was available for 66 (85.7 %) of these individuals at a mean of two years after acute stroke. On follow-up 64% (42/66) of the patients were alive and 45 % had had the FGT removed and resumed oral diets. On univariate analysis patients who were alive at the time of follow-up had received FGT feeding for a shorter period of time (p < 0.0003), showed no signs of aspiration on the Clinical Assessment of Feeding & Swallowing (CAFS,p < 0.020) and on the Videofluoroscopic Swallowing Study (VSS, 0.001), had a better discharge FIM-Score (Functional Independence Measure) for eating (p < 0.0002) and cognitive function (p < 0.002) as well as better discharge FCM-Score (Functional Communication Measure) for swallowing (p < 0.0001). On multivariate analysis we developed a model consisting of FGT removal at discharge from the rehabilitation hospital (p < 0.011) and non-aspiration during VSS (p < 0.040) that was significantly associated with longer survival time during follow-up. CONCLUSIONS: Severe dysphagia requiring FGT is common in patients with stroke referred for neurorehabilitation. Patients who had a FGT in place at the time of discharge from the stroke rehabilitation unit or aspirated during VSS were substantially more likely to have died by the time of follow-up compared to those who had had the FGT removed and had no signs of aspiration on VSS. However functional outcome measurements (FIM, FCM) including the cognitive function (attention, concentration etc.) could play an important role for prediction of swallowing regeneration and survival in neurorehabilitation. These findings may have practical utility in guiding physicians and speech language pathologists when advising patients and families about prognosis in stroke survivors with severe dysphagia.

Aged↗
PubMed2005

Functional neuroimaging and cognitive rehabilitation for people with traumatic brain injury.

Cognitive deficits are a common consequence of traumatic brain injury. Although such deficits are amenable to rehabilitation, methods for individualizing cognitive interventions are still unrefined. Functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging are emerging as possible technologies for measuring and monitoring the cerebral consequences of plasticity associated with brain injury and for evaluating the effectiveness of rehabilitation interventions. Functional neuroimaging may even enable more customized and efficient selection, design, or adaptation of individual cognitive rehabilitation programs. We review the current literature on functional neuroimaging after traumatic brain injury, relating these findings to cognitive rehabilitation. Overall, functional neuroimaging after traumatic brain injury has shown reliable differences in brain activity within several regions of frontal cortex, partly but not uniformly consistent with neuropsychological and structural findings in traumatic brain injury. We also outline a number of promising research opportunities for applying functional neuroimaging in traumatic brain injury settings, along with associated challenges.

Brain Injuries↗
PubMed2004

Compensation and advancement of women in academic medicine: is there equity?

BACKGROUND: Women have been entering academic medicine in numbers at least equal to their male colleagues for several decades. Most studies have found that women do not advance in academic rank as fast as men and that their salaries are not as great. These studies, however, have typically not had the data to examine equity, that is, do women receive similar rewards for similar achievement? OBJECTIVE: To examine equity in promotion and salary for female versus male medical school faculty nationally. DESIGN: Mailed survey questionnaire. SETTING: 24 randomly selected medical schools in the contiguous United States. PARTICIPANTS: 1814 full-time U.S. medical school faculty in 1995-1996, stratified by sex, specialty, and graduation cohort. MEASUREMENTS: Promotion and compensation of academic medical faculty. RESULTS: Among the 1814 faculty respondents (response rate, 60%), female faculty were less likely to be full professors than were men with similar professional roles and achievement. For example, 66% of men but only 47% of women (P < 0.01) with 15 to 19 years of seniority were full professors. Large deficits in rank for senior faculty women were confirmed in logistic models that accounted for a wide range of other professional characteristics and achievements, including total career publications, years of seniority, hours worked per week, department type, minority status, medical versus nonmedical final degree, and school. Similar multivariable modeling also confirmed gender inequity in compensation. Although base salaries of nonphysician faculty are gender comparable, female physician faculty have a noticeable deficit (-11,691 dollars; P = 0.01). Furthermore, both physician and nonphysician women with greater seniority have larger salary deficits (-485 dollars per year of seniority; P = 0.01). LIMITATIONS: This is a cross-sectional study of a longitudinal phenomenon. No data are available for faculty who are no longer working full-time in academic medicine, and all data are self-reported. CONCLUSIONS: Female medical school faculty neither advance as rapidly nor are compensated as well as professionally similar male colleagues. Deficits for female physicians are greater than those for nonphysician female faculty, and for both physicians and nonphysicians, women's deficits are greater for faculty with more seniority.

Career Mobility↗
PubMed2004

Evaluation of patients with severe pulmonary disease before and after pulmonary rehabilitation.

PURPOSE: The purpose was to evaluate the impact of inpatient pulmonary rehabilitation program upon changes in anxiety, depression, psychological outlook, and dyspnea. A secondary purpose was to predict changes in psychological outlook, depression, anxiety, and dyspnea by using three pulmonary function tests and age. METHODS: The design consisted of an observational study with pre-post comparisons. Forty-five patients with severe pulmonary disease, mean age 67.4 years (SD 9.2), mean FEV(1)=31.44% predicted, 13 men, 32 women were compared on four measures before and after 3 weeks of rehabilitation. Measures were Beck Depression Inventory, Hamilton Anxiety Scale, Goldberg Scale, and Modified Borg Scale. In addition, a linear multiple regression model using age, gender, % predicted FEV(1), FEV(1)/FVC, % predicted DLCO as independent variables were used to predict changes. RESULTS: Patients who completed the pulmonary program showed significant changes in favour of post scores on all four scales at p<0.001. The program significantly reduced anxiety and depression, and increased positive psychological outlook in severe pulmonary disease. Perceived breathlessness on the Borg Scale was significantly reduced (p<0.0001). The multiple regression model was not statistically significant for prediction of any of the changes. CONCLUSIONS: Patients with severe pulmonary disease can significantly improve their psychological outlook and decrease anxiety and depression when they complete an inpatient pulmonary rehabilitation program. Psychological gains and perception of breathlessness improve with rehabilitation, even though FEV(1) and other pulmonary function tests may not predict these changes. A second implication is that rehabilitation improves psychological outlook with both severely ill patients and a group with mixed pulmonary and cardiac disease.

Aged↗
PubMed2004

Clinician influences on use of portable electronic memory devices in traumatic brain injury rehabilitation.

PRIMARY OBJECTIVE: To explore the relationship between a group of clinicians' own experience, training and confidence with portable electronic memory devices and their use of the same in traumatic brain injury (TBI) rehabilitation. RESEARCH DESIGN: Survey study. METHODS AND PROCEDURES: Eighty-one TBI clinicians from various disciplines and work settings completed a survey distributed in person or by mail. MAIN OUTCOMES AND RESULTS: Twenty-nine respondents (36%) reported using portable electronic memory devices with patients with TBI. Using regression analysis, respondent device training and confidence teaching patients device use were statistically associated with respondents' use of such devices in TBI rehabilitation. CONCLUSIONS: Portable electronic memory device use with persons following TBI may be under-utilized. The importance of ongoing clinician training and of maximizing clinician confidence utilizing these devices in TBI rehabilitation is emphasized. The representativeness of the respondent sample is discussed. Specific training strategies and continued research needs are presented.

Adult↗
PubMed2003

Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media.

Otitis media, a common and often recurrent bacterial infection of childhood, is a major reason for physician visits and the prescription of antimicrobials. Haemophilus influenzae is the cause of approximately 20% of episodes of bacterial otitis media, but most strains lack the capsule, a factor known to play a critical role in the virulence of strains causing invasive H. influenzae disease. Here we show that in capsule-deficient (nontypeable) strains, sialic acid, a terminal residue of the core sugars of H. influenzae lipopolysaccharide (LPS), is a critical virulence factor in the pathogenesis of experimental otitis media in chinchillas. We used five epidemiologically distinct H. influenzae isolates, representative of the genetic diversity of strains causing otitis media, to inoculate the middle ear of chinchillas. All animals developed acute bacterial otitis media that persisted for up to 3 wk, whereas isogenic sialic acid-deficient mutants (disrupted sialyltransferase or CMP-acetylneuraminic acid synthetase genes) were profoundly attenuated. MS analysis indicated that WT bacteria used to inoculate animals lacked any sialylated LPS glycoforms. In contrast, LPS of ex vivo organisms recovered from chinchilla middle ear exudates was sialylated. We conclude that sialylated LPS glycoforms play a key role in pathogenicity of nontypeable H. influenzae and depend on scavenging the essential precursors from the host during the infection.

Animals↗
PubMed2003

High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae.

Non-typeable (NT) or capsule-deficient, Haemophilus influenzae (Hi) is a common commensal of the upper respiratory tract of humans and can be pathogenic resulting in diseases such as otitis media, sinusitis and pneumonia. The lipopolysaccharide (LPS) of NTHi is a major virulence factor that displays substantial intra-strain and inter-strain variation of its oligosaccharide structures. To investigate the genetic basis of LPS variation we sequenced internal regions of each of seven genes required for the biosynthesis of either the inner or the outer core oligosaccharide structures. These sequences were obtained from 25 representative NTHi isolates from episodes of otitis media. We found abundant evidence of recombination among LPS genes of NTHi, a finding in marked contrast to previous analyses of biosynthetic genes for capsular polysaccharide, a well-documented virulence factor of Hi. We found mosaic sequences, linkage equilibrium between loci and a lack of congruence between gene trees. These high rates were not confined to LPS genes since evidence for similar amounts of recombination was also found in eight housekeeping genes in a subset of the same 25 isolates. These findings provide a population based foundation for a better understanding of the role of NTHi LPS as a virulence factor and its potential as a candidate vaccine.

Genes, Bacterial↗
PubMed2003

Effects of methylphenidate on heart rate and blood pressure among inpatients with acquired brain injury.

OBJECTIVE: The purpose of this study was to evaluate the effects of methylphenidate on heart rate and blood pressure in patients with acquired brain injury. DESIGN: The records of 60 consecutive hospitalized patients with acquired brain injury were reviewed for treatment with methylphenidate. Seventeen patients met the inclusion criteria. Systolic blood pressure, diastolic blood pressure, and heart rate recordings were compared before and after the introduction of methylphenidate. RESULTS: There was no significant difference in mean systolic blood pressure, diastolic blood pressure, and heart rate when patients received (118 mm Hg, 74 mm Hg, and 88 bpm) and did not receive (118 mm Hg, 73 mm Hg, and 86 bpm) methylphenidate. It was unclear whether there was a true trend toward medication effect on heart rate and blood pressure during the peak dose period. CONCLUSIONS: This retrospective study points to safe sympathetic effects of methylphenidate, yet future prospective studies are warranted to clarify the effects of methylphenidate on heart rate and blood pressure in the acquired brain injury population.

Adult↗
PubMed2003

Characterization of encapsulated and noncapsulated Haemophilus influenzae and determination of phylogenetic relationships by multilocus sequence typing.

A multilocus sequence typing (MLST) scheme has been developed for the unambiguous characterization of encapsulated and noncapsulated Haemophilus influenzae isolates. The sequences of internal fragments of seven housekeeping genes were determined for 131 isolates, comprising a diverse set of 104 serotype a, b, c, d, e, and f isolates and 27 noncapsulated isolates. Many of the encapsulated isolates had previously been characterized by multilocus enzyme electrophoresis (MLEE), and the validity of the MLST scheme was established by the very similar clustering of isolates obtained by these methods. Isolates of serotypes c, d, e, and f formed monophyletic groups on a dendrogram constructed from the differences in the allelic profiles of the isolates, whereas there were highly divergent lineages of both serotype a and b isolates. Noncapsulated isolates were distinct from encapsulated isolates and, with one exception, were within two highly divergent clusters. The relationships between the major lineages of encapsulated H. influenzae inferred from MLEE data could not be discerned on a dendrogram constructed from differences in the allelic profiles, but were apparent on a tree reconstructed from the concatenated nucleotide sequences. Recombination has not therefore completely eliminated phylogenetic signal, and in support of this, for encapsulated isolates, there was significant congruence between many of the trees reconstructed from the sequences of the seven individual loci. Congruence was less apparent for noncapsulated isolates, suggesting that the impact of recombination is greater among noncapsulated than encapsulated isolates. The H. influenzae MLST scheme is available at www.mlst.net, it allows any isolate to be compared with those in the MLST database, and (for encapsulated isolates) it assigns isolates to their phylogenetic lineage, via the Internet.

Bacterial Capsules↗
PubMed2002

Cutoff score on the apathy evaluation scale in subjects with traumatic brain injury.

This cross-sectional study was designed to determine a cutoff score on the Apathy Evaluation Scale (AES) that predicts a clinician's designation of a subject with TBI as apathetic or not. Forty-five outpatients with TBI completed the AES-S, and 37 family members, friends, or significant others filled out the AES-I. Three clinicians prospectively gave their impressions of the presence or absence of apathy and retrospectively chose the degree of apathy on a 7-point subjective rating scale. The data was analysed by logistic regression and Receiver Operating Characteristic (ROC) curve. Sensitivity and specificity were calculated. No cutoff score on the AES-S or AES-I was found to have reasonable sensitivity and specificity with respect to the ability to predict the clinician's designation of a subject as apathetic. The AES requires further study if it is to be used to measure apathy following TBI.

Adolescent↗