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Biomedical subjects

R Herman

Publications and source records attributed to R Herman.

At least 19 recordsLinked to original sources

The 2.4-A crystal structure of the penicillin-resistant penicillin-binding protein PBP5fm from Enterococcus faecium in complex with benzylpenicillin.

Penicillin-binding proteins (PBPs) are membrane proteins involved in the final stages of peptidoglycan synthesis and represent the targets of beta-lactam antibiotics. Enterococci are naturally resistant to these antibiotics because they produce a PBP, named PBP5fm in Enterococcus faecium, with low-level affinity for beta-lactams. We report here the crystal structure of the acyl-enzyme complex of PBP5fm with benzylpenicillin at a resolution of 2.4 A. A characteristic of the active site, which distinguishes PBP5fm from other PBPs of known structure, is the topology of the loop 451-465 defining the left edge of the cavity. The residue Arg464, involved in a salt bridge with the residue Asp481, confers a greater rigidity to the PBP5fm active site. In addition, the presence of the Val465 residue, which points into the active site, reducing its accessibility, could account for the low affinity of PBP5fm for beta-lactam. This loop is common to PBPs of low affinity, such as PBP2a from Staphylococcus aureus and PBP3 from Bacillus subtilis. Moreover, the insertion of a serine after residue 466 in the most resistant strains underlines even more the determining role of this loop in the recognition of the substrates.

Amino Acid Sequence↗

Spinal cord stimulation facilitates functional walking in a chronic, incomplete spinal cord injured.

DESIGN: This paper describes a treatment paradigm to facilitate functional gait in a quadriplegic, ASIA C spinal cord injured (SCI), wheelchair-dependent subject who presented with some large fiber sensation, sub-functional motor strength in all lower limb muscles, and moderate spasticity. The study utilizes partial weight bearing therapy (PWBT) followed by epidural spinal cord stimulation (ESCS) with the assumption that both treatments would be necessary to elicit a well organized, near effortless functional gait with a walker. Function is defined in terms of accomplishing task-specific activities in the home and community. OBJECTIVES: To demonstrate the feasibility and benefits of combined PWBT and ESCS therapies aimed at promoting functional gait in a wheelchair-dependent ASIA C SCI subject. SETTING: The Clinical Neurobiology and Bioengineering Research Laboratories at Good Samaritan Regional Medical Center, Phoenix, Arizona, USA, and the Department of Bioengineering, Arizona State University, Tempe, Arizona, USA. METHODS: The study began with the application of PWBT. The subject walked on the treadmill until a plateau in gait rhythm generation was reached. Subsequently, ESCS, applied to the lumbar enlargement, was utilized to facilitate PWBT and, later, over-ground walking for a standard distance of 15 m. Gait performance was analyzed by measuring average speed, stepping symmetry, sense of effort, physical work capacity, and whole body metabolic activity. RESULTS: PWBT led to improved stereotypic stepping patterns associated with markedly reduced spasticity, but was insufficient for over-ground walking in terms of safety, energy cost, and fatigue. ESCS with PWBT generated immediate improvement in the subject's gait rhythm when appropriate stimulation parameters were used. When compared to the non-stimulated condition, over-ground walking with ESCS across a 15 m distance was featured by a reduction in time and energy cost of walking, sense of effort, and a feeling of 'lightness' in the legs. After a few months of training, performance in speed, endurance, and metabolic responses gradually converged with/without ESCS at this short distance, suggesting a learned response to these conditions. However, at longer distances (eg, 50-250 m), performance with ESCS was considerably superior. The subject was able to perform multiple functional tasks within the home and community with ESCS. CONCLUSION: We propose that ESCS augments the use-dependent plasticity created by PWBT and may be a valuable adjunct to post-SCI treadmill training in ASIA C subjects. We also conclude that ESCS elicits greater activation of an oxidative motor unit pool, thereby reducing the subject's sense of effort and energetic cost of walking.

Adult↗

Evaluation of sporadic cases of odontogenic keratocysts in multicentric study.

The aim of this retrospective study was to report frequency of sporadic odontogenic keratocysts (sOKC) according to the age and gender, as well as location (mandible, maxilla, soft tissues, and maxillary sinus). Four hundred and twenty nine sOKC confirmed pathohistologically in a period from 1965-1998 were included in this study. The average age of patients with sOKC was 43.11 (age range 10-91), in males 42.06 and in females 44.72 years. More frequently sOKC were found in males (60.61%) in comparison to the females (39.39%). Therefore, ratio between males and females was 1.5:1. Diagnosis of sOKC is usually established in patients aged 21-30 (18.88%), in males usually aged between 21-30 (23.46%), and in females aged between 11-20 (18.93%). sOKC are more frequent in males according to the age groups, except between age 61-70 where sOKC were more frequent in females. Most frequently, sOKC occurred in the mandible 70.16%, 12.35% of sOKC were found in the maxilla, 12.82% in soft tissues and 4.66% in the maxillary sinuses.

Adolescent↗

Modified fetal biophysical profile in the assessment of perinatal outcome.

The aim of the study is the evaluation of variables of the biophysical profile in the assessment of perinatal outcome. The prospective study included 87 pregnant women with singleton pregnancy in the 28th to 42nd week of gestation with clinically and ultrasonically verified fetal growth retardation, where the fetal biophysical profile was assessed antenatally. Through the factor analysis of biophysical profile variables we obtained values indicating the contribution of individual variables to the predictability of perinatal outcome. 70% of the patients were examined in 15 minutes according to the principles of modified biophysical profile. The most sensitive variable of the biophysical profile in the prediction of perinatal outcome was the amniotic fluid volume, followed by fetal breathing movements, non-stress test and fetal movements, while the lowest prediction value was assigned to the fetal tone. The modified biophysical profiles need to be perfected on a larger number of pregnant women, which would advance the predictability of this method in detection of hypoxically endangered fetuses.

Female↗

Characterization of OXA-29 from Legionella (Fluoribacter) gormanii: molecular class D beta-lactamase with unusual properties.

A class D beta-lactamase determinant was isolated from the genome of Legionella (Fluoribacter) gormanii ATCC 33297(T). The enzyme, named OXA-29, is quite divergent from other class D beta-lactamases, being more similar (33 to 43% amino acid identity) to those of groups III (OXA-1) and IV (OXA-9, OXA-12, OXA-18, and OXA-22) than to other class D enzymes (21 to 24% sequence identity). Phylogenetic analysis confirmed the closer ancestry of OXA-29 with members of the former groups. The OXA-29 enzyme was purified from an Escherichia coli strain overexpressing the gene via a T7-based expression system by a single ion-exchange chromatography step on S-Sepharose. The mature enzyme consists of a 28.5-kDa polypeptide and exhibits an isoelectric pH of >9. Analysis of the kinetic parameters of OXA-29 revealed efficient activity (k(cat)/K(m) ratios of >10(5) M(-1) x s(-1)) for several penam compounds (oxacillin, methicillin, penicillin G, ampicillin, carbenicillin, and piperacillin) and also for cefazolin and nitrocefin. Oxyimino cephalosporins and aztreonam were also hydrolyzed, although less efficiently (k(cat)/K(m) ratios of around 10(3) M(-1) x s(-1)). Carbapenems were neither hydrolyzed nor inhibitory. OXA-29 was inhibited by BRL 42715 (50% inhibitory concentration [IC(50)], 0.44 microM) and by tazobactam (IC(50), 3.2 microM), but not by clavulanate. It was also unusually resistant to chloride ions (IC(50), >100 mM). Unlike OXA-10, OXA-29 was apparently found as a dimer both in diluted solutions and in the presence of EDTA. Its activity was either unaffected or inhibited by divalent cations. OXA-29 is a new class D beta-lactamase that exhibits some unusual properties likely reflecting original structural and mechanistic features.

Amino Acid Sequence↗

The communication, speech and gesture of a group of hearing-impaired children.

The communication skills, speech and gesture of 20 hearing-impaired children were assessed. The children were all being educated in a school using an oral/aural approach. Assessment result comparison indicated the importance of assessing gesture and speech separately for these children and comparing the use of both skills. More informal and formal assessment of gesture and the tools to complete this task effectively are needed to ensure that these children's communication skills are described accurately.

Child↗

The 2000 Canadian recommendations for the management of hypertension: Part one--therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that may control blood pressure. Randomized trials evaluating first- line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS, AND COSTS: Various lifestyle manoeuvres and antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to all aspects of the therapy of patients with hypertension, including lifestyle modifications proven to lower blood pressure, treatment thresholds, target blood pressures, choice of agents in various settings and strategies to enhance adherence. Lower thresholds for blood pressure treatment are advocated for people with other cardiovascular risk factors or established hypertensive target organ damage. Implicit in the recommendations for therapy is the principle that treatment should be individualized for each patient and the choice of agent should be dictated by coexistent conditions. For the treatment of uncomplicated essential hypertension, thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors or calcium channel blockers may be appropriate, depending on individual circumstances. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually.

Adult↗

Improved survival in severe acquired aplastic anemia of childhood.

Multi-agent immunosuppressive therapy has produced improved survival for severe acquired aplastic anemia in children. Recently, some investigators have suggested that immunosuppressive therapy may replace bone marrow transplantation as first-line therapy for this disorder. To assess its validity, we compared the outcomes of bone marrow transplantation vs immunosuppressive therapy in one institution from 1987 to 1997. We studied 46 consecutive patients less than 18 years of age who presented between January 1987 and April 1997. Inherited marrow failure syndromes and myelodysplastic syndromes were excluded. Patients received immunosuppressive therapy vs bone marrow transplantation based on availability of HLA-matched donors. The main outcome measures were survival, complete marrow and hematological remission, or partial remission but achieving independence from transfusional support. Twenty patients received multi-agent immunosuppressive therapy (cyclosporine, antithymocyte globulin and methylprednisolone); 11 attained complete remission and three partial remission for a transfusion-independent survival of 70%. Six patients died of infectious and hemorrhagic complications. Twenty-six patients were transplanted and 24 (93%) achieved complete remission; one achieved a PR, 25 remain transfusion independent with a median follow-up of 5.9 years or 70 months. One patient developed AML 34 months after successful transplant and one patient died due to graft failure and complications of transplant. There has been a striking improvement in survival for pediatric patients treated with multi-agent immunosuppression in the last decade. However, transplantation results have also improved and this remains the definitive first-line therapy for severe acquired aplastic anemia in this age group.

Adolescent↗

The influence of global discourse on lexical ambiguity resolution.

The influence of global discourse on the resolution of lexical ambiguity was examined in a series of naming experiments. Two-sentence passages were constructed to bias either the dominant or the subordinate meaning of a homonym that was embedded in a locally ambiguous sentence. The results provided evidence for the immediate (0-msec interstimulus interval) resolution of lexical ambiguity and were subsequently replicated in Experiment 2, in which an 80-msec stimulus onset asynchrony exposure duration was employed for the homonyms. Strong dominant and subordinate biased discourse contexts activated only the contextually appropriate sense of a homonym. In Experiment 3, each sentence of the discourse was presented in isolation. The pattern of activation obtained in Experiments 1 and 2 was found to be contingent on the integration of the two sentences to construct an overall global discourse representation of the text. The results support a context-sensitive model of lexical ambiguity resolution.

Cognition↗

[Fetal hypoxia--etiology and pathophysiology of hypoxic damage].

In current perinatology, the prevention of hypoxic damage to the organs, brain in particular, is given special emphasis. The causes of fetal hypoxia include maternal (preuterine), intrauterine, umbilical, placental and fetal causes. Hypoxia and hypoxic lesions occur prenatally in about 80%, and perinatally in 10-20% of cases. Hypoxia/ischemia induce cellular and subcellular responses in the fetal brain. Some of these are membraneous phenomena such as potassium channel activation, enhanced release of excitoxic amino acids aspartate and glutaminate, activation of NMDA receptors, transmembranous calcium ion influx, and membranous lipid peroxidation. Cytosolic events include the formation of free oxygen radicals, release of eicosanoids, prostaglandins, leukotriens and cytokines, enzyme activation, and gene induction.

Female↗

AIDS-related services and training in outpatient mental health care agencies in New York.

Directors of 471 outpatient mental health settings in New York State (82.1 percent of 574 settings located in counties with intermediate to high AIDS case rates) completed a survey about HIV and AIDS services, training needs, and barriers to care. Most of the sites served one to ten persons with HIV infection annually and had staff members who were trained in providing at least one HIV-related service. Nonetheless, 84 percent of the respondents reported unmet needs for training. The likelihood of providing certain services was significantly increased in sites that were in urban locations, primarily served clients with comorbid alcohol or other drug use disorders, lacked funds for providing condoms, had staff members who were trained in HIV and AIDS services, identified particular HIV training needs, believed clients needed condoms, and viewed HIV-related services as very important.

Acquired Immunodeficiency Syndrome↗

Preoperative tumor marker CA125 levels in relation to epithelial ovarian cancer stage.

The paper deals with 62 ovarian cancer patients observed from 1988 to 1997. Considering the ovarian cancer stage, the patients were divided in two groups. Group I consisted of 31 patients at the early stage of ovarian carcinoma (FIGO classification I and II), while group II included 31 patients with the advanced disease (FIGO classification III and IV). According to FIGO classification, a majority of group I and group II patients was classified as IA (61.3%) and IIIC, respectively. Ovarian carcinoma of the serous pathohistologic type accounting for 48.4% prevailed in both groups, but there were also endometroid and mucinous types. Sensitivity to CA125 was observed in 93.5% of the group I and in 96.7% of the group II patients. In group I, the mean value of tumor marker CA125 read 262.97 U/ml, median 93 U/ml, ranging from 13-2000 U/ml. In comparison with group I, the mean value of group II tumor marker CA125 was significantly higher reading 1053.81 U/ml, median 365 U/ml, with CA125 levels ranging from 15-9960 U/ml. In relation to patients at the early stage of ovarian cancer, preoperative CA125 serum levels were statistically more significant in the advanced ovarian cancer patients (statistically significant difference p = 0.002). When comparing CA125 levels and tumor differentiation according to Broders, no statistically significant difference was observed in both group I (p = 0.6144) and group II (p = 0.6605). The statistically significant correlation (p = 0.00008) was confirmed between advanced ovarian carcinoma and less differentiated tumors (Broders differentiation III and IV).

CA-125 Antigen↗

Issues in designing an assessment of British Sign Language development.

This paper reports on a collaborative project in progress to develop a standardised clinical assessment of British Sign Language development for use with deaf children. The need for such an assessment is highlighted following a survey of professionals working in this area (Herman, in press). The development of the assessment battery will be described in the context of research into the assessment of sign language development. Issues in selection of the standardisation population will be presented. Finally the need for collaboration between different professionals working in this area, in particular the key role of the deaf BSL user will be emphasised.

Child↗

Effects of early defibrillation by ambulance personnel on short- and long-term outcome of cardiac arrest survival: the Munich experiment.

OBJECTIVES: This study evaluates the feasibility of implementing early defibrillation of out-of-hospital cardiac arrest patients for basic life-support providers (EMT-D) in a two-tier emergency system in the city of Munich, Germany. DESIGN: Retrospective consecutive analysis of all EMT-D attempts during a 5-year initiation phase (1990 to 1994) and prospective follow-up of all cardiac arrest survivors discharged from hospital. SETTING: A strictly defined inner-city and suburban area of 978 km2 and a residential population of 1,530,000 inhabitants with 22 ICUs in urban hospitals. One dispatching center to alert a two-tier emergency system with 56 EMT-D-staffed ambulances and physician-staffed mobile ICUs stationed at the nearest of nine hospitals. METHODS: AH EMT-D cases were identified and data on patients were documented in a standardized manner from patients' records, including the resuscitation protocol in the hospitals to which the patients were referred. For those patients discharged from the hospital, a standardized telephone interview was undertaken with the physician in charge of the patient and with the patient/relative leading to an assessment of the patient's status according to the Glasgow-Pittsburgh cerebral performance categories. INTERVENTION: None. RESULTS: During the 5-year initiation phase of the EMT-D program in the two-tier emergency system in Munich, there were 243 resuscitation attempts by EMTs, using the semiautomated defibrillator; 125 patients died immediately on the scene. In 118 patients, spontaneous circulation was reestablished and these patients were admitted to an ICU in 1 of the 22 urban hospitals. Median call-response interval for the EMT-D was 5 min (interquartile range, 3 to 6) and was 10 min (interquartile range, 7 to 13) for the second tier (p < or = 0.0001). In 34 cases (28.8%), EMT-D staff had reestablished spontaneous circulation (ROSC) before the second tier arrived on the scene. Patients with ROSC on the arrival of the second tier were more frequently discharged alive from hospital than were patients without ROSC at that time (p < or = 0.0001). The hospital discharge rate of initially successful resuscitated patients presenting with out-of-hospital ventricular fibrillation was 38.1% (45/118). Overall success rate of all EMT-D attempts was 18.5% (45/243). After a mean follow-up time of 39 (range, 22 to 64) months, 29 (66%) patients were still living. Twenty-five (56.8%) were neurologically not disabled or mildly disabled (CPC 1/2); disability was moderate in 3 (6.8%) patients and was severe in 1 (2.3%) patient. One case was lost to follow-up. CONCLUSION: The present study demonstrates that the upgrading of basic life support providers with semiautomated defibrillators has a significant benefit for cardiac arrest victims outside the hospital in an urban environment.

Ambulances↗