Variability of total phenytoin serum concentrations within elderly nursing home residents.

BACKGROUND: Approximately 6% of all elderly nursing home residents receive phenytoin. Phenytoin concentrations are often measured to guide therapy. OBJECTIVE: To evaluate the intraresident variability among multiple measurements of total phenytoin serum concentrations in nursing home residents. METHODS: This was an observational study of 56 elderly (>or=65 years) nursing home residents from 32 nursing homes who had at least 3 phenytoin concentrations measured while on the same dose of phenytoin for at least 4 weeks and who were not taking any interfering concomitant medications. These were a subset of 387 elderly nursing home residents from 112 nursing homes across the United States who had total phenytoin concentration measurements between June 1998 and December 2000. RESULTS: The mean age was 80.1 years (range, 65 to 100 years) and 58.9% were women. The mean daily dose of phenytoin per resident was 4.9 +/- 1.5 mg/kg. Total phenytoin concentrations within an elderly nursing home resident varied as much as two- to threefold, even though there was no change in dose. The person with the smallest variability had a minimum concentration of 10.0 micro g/mL and a maximum of 10.4 micro g/mL. The person with the largest variability had a minimum concentration of 9.7 micro g/mL and a maximum of 28.8 micro g/mL. CONCLUSIONS: There is considerable variability in the total phenytoin concentrations in the elderly nursing home resident and measurement of a single total phenytoin concentration should not be used to guide treatment.

Electrical stimulation of the auditory nerve: single neuron strength-duration functions in deafened animals.

Destruction of cochlear hair cells initiates degenerative changes within auditory nerve fibres (ANFs), including loss of peripheral processes and demyelination of the cell body. These changes are likely to affect the biophysical processes involved in action potential generation to an electrical stimulus. We measured the strength-duration relationship in acutely deafened (100% ANF survival) versus long-term deafened cochleae (approximately 15% ANF survival) by recording from single neurons in the central nucleus of the inferior colliculus (ICC). Input/output functions were constructed for 22 ICC neurons in response to stimulation of the auditory nerve using biphasic current pulses of 20-1000 micros/phase. Strength-duration curves were derived and found to be of the same general form for both acute and long-term deafened cochleae. While there was an increase in rheobase for neurons from long-term versus acute deafened cochleae, this increase was not statistically significant (p=0.097). In contrast, chronaxie--which is related to the membrane time constant--was significantly shorter in the long-term deafened cochleae (p = 0.004). This presumably reflects a shift in the site of action potential initiation to the larger diameter, heavily myelinated central axon as a result of the pathology. These changes in the site of action potential generation have implications for the delivery of charge to ANFs via cochlear implants.

Deafness-induced changes in the auditory pathway: implications for cochlear implants.

A profound sensorineural hearing loss induces significant pathological and atrophic changes within the cochlea and central auditory pathway. We describe these deafness-induced morphological and functional changes following controlled lesions of the cochlea in experimental animals. Such changes are generally consistent with the limited number of reports describing deafness-induced changes observed in human material. The implications of these pathophysiological changes within the auditory pathway on cochlear implant function are discussed. Finally, the plastic response of the deafened auditory system to electrical stimulation of the auditory nerve is reviewed in light of the clinical implications for cochlear implant recipients.

Factors associated with antiepileptic drug use among elderly nursing home residents.

UNLABELLED: BACKGROUND. Epilepsy, a chronic condition defined as two or more recurrent, unprovoked seizures, has the highest incidence at the end of life. Antiepileptic drugs (AEDs) are the primary therapeutic mode. Approximately 10%-11% of elderly nursing home residents receive one or more AEDs, a higher prevalence than would be expected in this age group. In the research literature, there is not a clear explanation of variations in AED use in nursing homes. The purpose of this study was to examine the prevalence and variations in use of AEDs by resident characteristics, AEDs used, drug dosage, and AED combinations in treatment regimens. METHODS: This was a retrospective, cross-sectional study of residents (N = 21,551) in a convenience sample of nursing homes in 24 states and the District of Columbia. The unit of analysis was the individual resident. The study period was a single day in 1995. Bivariate and multivariate analyses were used to test differences. RESULTS: The prevalence of AED use was 10.5% across all elderly residents. In a multivariate analysis, factors associated with AED treatment included seizure indication, age group, and geographic region. AED use by age group showed declining use as the residents aged, from 65-74 to 75-84 to > or =85 years. CONCLUSIONS: The inverse relationship between AED use and age group was unexpected because the incidence of epilepsy increases with advancing age. This finding raises important questions about the future use of these drugs in elderly nursing home residents.

Neonatal sensorineural hearing loss affects neurone size in cat auditory midbrain.

We examined the effect of a neonatal sensorineural hearing loss on the soma area of neurones in the central nucleus of the inferior colliculus (ICC) in adult cats to evaluate the role of auditory experience on neuronal atrophy within the auditory midbrain. Three groups of animals were used: bilaterally deafened, unilaterally deafened and normal hearing controls. Soma area measurements were made from the laminated central and medial divisions of the ICC of eight deafened and two normal hearing cats. A small but significant reduction in soma area was evident for bilaterally deafened animals compared with normal hearing controls (P<0.05, Dunnett's test). In contrast, there was no significant difference in mean soma area between normal hearing and unilaterally deafened animals (P0.05) irrespective of whether the ICC examined was ipsi- or contralateral to the deafened ear. These results demonstrate that the reduction in soma area of auditory brainstem neurones reported following a sensorineural hearing loss is also evident at the level of the auditory midbrain.

Response of inferior colliculus neurons to electrical stimulation of the auditory nerve in neonatally deafened cats.

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1-2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 micros/phase biphasic current pulses. Single-unit (n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10-25 ms) compared with those in the ICC (5-8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.

Sensorineural hearing loss during development: morphological and physiological response of the cochlea and auditory brainstem.

We have investigated the effects of sensorineural hearing loss on the cochlea and central auditory system of profoundly deafened cats. Seventeen adult cats were used: four had normal hearing; 12 were deafened neonatally for periods of < 2.5 years (five bilaterally, seven unilaterally); and one animal had a long-term (approximately 8 years) profound bilateral hearing loss. Bipolar scala tympani stimulating electrodes were bilaterally implanted in each animal, and electrically evoked auditory brainstem responses (EABRs) were recorded in an acute study to evaluate the basic physiologic response properties of the deafened auditory pathway. The cochleae and cochlear nuclei (CN) of each animal were examined with light microscopy. Spiral ganglion cell density in neonatally deafened cochleae was 17% of normal, and only 1.5% of normal in the long-term deaf animal. There was a 46% reduction in total CN volume in neonatally deafened animals compared to normal, and a 60% reduction in the long-term deaf animal. Neural density in the anteroventral CN of bilaterally deafened animals was 37% higher than normal; 44% higher in the long-term deaf animal. Significantly, however, we saw no evidence of a loss of neurones within the anteroventral CN in any deafened animal. There was a significant increase in EABR threshold and wave IV latency in the deafened animals, and a significant decrease in response amplitude and input/output function gradient. Again, these changes were more extensive in the long-term deaf animal. These data show that a sensorineural hearing loss can evoke significant morphological and physiological changes within the cochlea and auditory brainstem, and these changes become greater with duration of deafness. It remains to be seen whether these changes can be reversed following the introduction of afferent activity via chronic electrical stimulation of the auditory nerve.

Neonatal sensorineural hearing loss affects synaptic density in the auditory midbrain.

We examined the effect of neonatal sensorineural hearing loss on synaptic density in the central nucleus of the inferior colliculus (ICC) of adult cats to evaluate the role of auditory experience in synaptogenesis. Three groups of animals were used: bilaterally deafened, unilaterally deafened and normal hearing controls. Synaptic density in bilaterally deafened animals was significantly lower than in normal hearing animals. By contrast, there was no significant difference in synaptic density between normal hearing animals and unilaterally deaf animals. These results demonstrate, for the first time, that a sensorineural hearing loss during development can affect synaptogenesis in the auditory midbrain.

The consequences of deafness and chronic intracochlear electrical stimulation on the central auditory pathways.

1. Auditory deprivation can result in significant morphological and physiological changes within the central auditory nervous system. These changes are generally more pronounced when the onset of deafness occurs early in development, as is the case with congenitally deaf children. 2. A review of the auditory plasticity literature suggests that some of these deafness-induced changes may be preventable or partially reversible by electrical stimulation of the auditory nerve. 3. With the increasing application of cochlear implants in congenitally deaf children, it is important to evaluate the consequences of introducing electrical stimulation to the developing auditory nervous system.

Incidence of orofacial injuries in high school sports.

OBJECTIVES: This study determined the incidence of orofacial injuries in athletes attending seven neighboring Minnesota high schools who participated in varsity soccer, wrestling, and basketball during the 1996-97 academic year. METHODS: Incidence was determined through athletes' written surveys and athletic trainer records. RESULTS: Survey response rates ranged from 86.3 percent to 94.0 percent among schools for all sports. The incidence rate of at least one orofacial injury per athlete in a season was 27.6 percent (SD = 20.2) in soccer, 72.3 percent (SD = 9.3) in wrestling, and 55.4 percent (SD = 23.9) in basketball. Ten percent of athletes sustained dental injuries. Fixed orthodontic appliances posed a higher risk for sustaining an injury in all sports. The games-to-practices ratios for injuries were 6.8 (soccer), 1.2 (wrestling), and 1.8 (basketball). Half of the athletes believed mouthguards prevent injuries; however, only 6 percent of the athletes reported mouthguard use. Athletic trainers reported eight orofacial injuries. CONCLUSIONS: The substantial rate of orofacial injuries among high school athletes participating in soccer, wrestling, and basketball needs to be minimized. Dentists should ask their adolescent patients routinely about sports participation. Policies should be developed to require school officials to report orofacial injuries, to inform athletes of their risk for orofacial injuries, and to consider mandated mouthguard use for these athletes.

Broth disk elution method for anaerobic bacteria: a collaborative study to assess its reliability for clinical purposes.

A collaborative study involving seven laboratories was undertaken to evaluate the reproducibility and the reliability of the broth disk elution test against anaerobic bacteria by comparing with the reference agar dilution method. A two breakpoint broth test was also evaluated. Assays were performed using the same testing conditions (i.e. medium, temperature, atmosphere and incubation time). One hundred Gram-negative and Gram-positive clinical isolates were initially studied. Overall agreement of 98.5% and 97.5%, were found for disk elution and the two breakpoint tests, respectively. In order to assess the reliability of the disk elution test, two different lots (LOT1 and LOT2) of disks of piperacillin and clindamycin were selected, to obtain two final concentrations after dilution (10 and 60 mg/mL; 1 and 4 mg/mL, respectively). Two hundred and eighty assays were performed against one strain of both Bacteroides fragilis(piperacillin MIC, 8.0 mg/mL; clindamycin MIC, <0.5 mg/mL) and Bacteroides thetaiotaomicron(piperacillin MIC, 16.0 mg/mL; clindamycin MIC, <0.5 mg/mL). With LOT 1, considering both species and both antibiotics, the agreement among six laboratories ranged from 85% to 100% (P > 0.05) with the higher concentration. Overall agreement among all laboratories was 91%. No optimal agreement (>90%) for clindamycin-Bacteroides thetaiotaomicron using the LOT1 (77%) was found. Since this finding was not observed with LOT2 (100% agreement), discrepancies were attributed to variation between lots. Overall agreement with LOT2 was 100% for all centres. The present study indicates that the broth disk elution method proved to be a reliable and suitable alternative for routine susceptibility testing for anaerobic bacteria, as a resistance screening method for clinical purposes.

Primary incisor decay before age 4 as a risk factor for future dental caries.

The purpose of this investigation was to determine whether early childhood caries (ECC) is a risk factor for future dental caries. One hundred fifteen dental charts of children younger than 4 years of age when initially treated were reviewed and abstracted for primary incisor caries and age at the initial examination, gender, recall dental visits, sealants, and age at the last dental examination. In addition, the number of carious, extracted, and restored teeth (cert/CERT: primary/secondary) at the last examination was determined. Children with ECC at their initial examination (N = 58) had a 93.0% cert rate, a 67.2% CERT rate and a 60.3% CERT in first molars rate by their last dental examination. Non-ECC children at their initial examination (n = 57) had less than half the rate of each cert/CERT parameter (43.9%, 22.8%, and 26.3%, respectively) at their last dental visit. The odds ratios for each cert/CERT parameter posed by ECC status were 17.3 for cert, 7.0 for CERT, and 4.3 for CERT in first molars. When these odds were adjusted for other study parameters by a forward step-wise logistic regression analysis, ECC status continued to be a risk factor for each cert/CERT parameter. We conclude that 1) early childhood caries is a risk factor for future caries, 2) increased age is a risk factor for CERT, and 3) recalls and sealants are protective factors.

The central auditory system and auditory deprivation: experience with cochlear implants in the congenitally deaf.

In the present paper we briefly review the response of the central auditory system to auditory deprivation and describe recent experimental and clinical experience with cochlear implants. While the central auditory system undergoes marked changes in response to auditory deprivation, it would appear that at least a rudimentary cochleotopic organisation is maintained at the level of the brainstem and auditory cortex in animals deafened from birth. Moreover, recent studies have demonstrated the ability of the central auditory system to undergo functional reorganisation in response to changes in the pattern of afferent activity. Clinical experience has shown that deaf children with little or no prior auditory experience can obtain significant benefit from cochlear implants, provided the device is fitted at a young age. Furthermore, factors predicting successful clinical outcomes with these devices reflect the importance of auditory experience, either prior to an acquired loss or with the use of a cochlear implant. These findings suggest that functional reorganisation within the central auditory pathway can at least partially account for improvements in clinical performance over time.

Survey of the levels of antimicrobial resistance in Argentina: WHONET program--1991 to 1994.

The World Health Organization has implemented an international program of antibiotic resistance survey, called WHONET, with the participation of 121 laboratories from 41 countries around the world. Argentina joined WHONET program in 1989. Five hospitals from Buenos Aires are taking part, under the coordination of the National Institute of Microbiology 'Dr. C. Malbran'. From the results obtained between 1991 and 1994, the low level of susceptibility to aminopenicillins, cephalosporins and aminoglycosides is remarkable. On the other hand, vancomycin-resistant Enterococcus spp. and Staphylococcus spp. have not been detected and imipenem resistance in Pseudomonas aeruginosa, and Acinetobacter spp. isolates has not overcome 7% and 11%, respectively. Analytical programs utilizing these data aid in the understanding of the epidemiology of antibiotic resistance and in the development of rational antibiotic prescription practices and infection control procedures.

Intrasulcular laser Doppler readings before and after root planing.

A reproducible and sensitive laser Doppler periodontal probe has recently been developed for intrasulcular measurement of gingival blood flow. The specific aims of this investigation were to determine the relation between intrasulcular laser Doppler readings (LDR) and traditional diagnostic criteria as well as to evaluate the response to root planning in terms of LDR and traditional criteria. LDR and clinical measurements (bleeding on probing (BOP), probing depth (PD) and clinical attachment loss (CAL) were obtained from 2 healthy and 2 diseased sites in 30 systemically healthy adult volunteers with localized moderate to advanced periodontitis. All 30 subjects were re-examined 1 month following root planing while 10 subjects were re-examined at approximately 1 year after treatment. Subject-adjusted correlations between pretreatment LDR and PD as well as LDR and CAL were 0.74 and 0.71, respectively. 1 month following root planing, the diseased sites had undergone a significant reduction in LDR and PD with an accompanying gain in CAL. Prior to treatment, 95 of 120 sites (79%) agreed on an ordinal classification (high, low) for LDR and BOP. Mantel-Haenszel common odds ratios for agreement between LDR and BOP were 9.6 pre-treatment and 4.3 one month after treatment. A slight rebound of all measurements was noted in a group of 10 subjects followed for 1 year. It was concluded that the laser Doppler periodontal probe is an unbiased non-invasive method of monitoring the response to periodontal therapy.

Effect of gingival fluid collection on subgingival plaque sampling.

The purpose of this study was to determine whether gingival crevicular fluid (GCF) sampling by paper strip removes sufficient bacteria to affect subsequent subgingival plaque sampling using a curette. In 25 subjects, one healthy, gingivitis and periodontitis site was sampled for GCF using a strip followed by subgingival plaque sampling with a curette. Bacterial assays indicated that GCF strips removed significant numbers of bacteria when placed intracrevicularly for 5 s. A greater proportion of total bacteria was removed with strip sampling at healthy rather than gingivitis or periodontitis sites. Qualitative assessment of presence or absence of spirochaetes and dark-pigmented species indicated potential for significant interference of curette sampling by the strip at gingivitis and healthy sites. We concluded that paper strip GCF sampling may significantly affect curette sampling at the same sites. The magnitude of this impact depended on the clinical classification of specific sites and the assay performed.

Estudio multicéntrico de la sensibilidad de bacterias anaerobias en la Argentina / Multicentric study of anaerobic bacteria susceptibility in Argentina

Se determinó la actividad de ampicilina (AMP), ampicilina-sulbactama (AMS), penicilina (PEN), piperacilina (PIP), imipenem (IMI), cefoxitina (CXT), ceftizoxima (CFZ), clindamicina (CLI), cloranfenicol (CLO) y metronidazol (MET) frente a 106 cepas de bacterias anaerobias aisladas de muestras clínicas en seis centros asistenciales del país por un método de dilución en agar. Todos los microorganismos gramnegativos fueron sensibles a AMS, CLO, IMI y MET. Se encontraron 5/7 Bacteroides spp., 2/6 bacilos gram negativos pigmentados y 1/4 Fusobacterium spp. resistentes a AMP. Los Bacteroides del grupo fragilis fueron altamente resistentes a AMP y la especie Bacteroides fragilis fue más sensible a PIP, CXT, CFZ y CLI que las otras especies del grupo (5 por ciento vs. 21 por ciento, 5 por ciento vs. 7 por ciento, 8 por ciento vs. 14 por ciento y 2,5 por ciento vs. 14 por ciento respectivamente). Entre los organismos gram positivos se encontró resistencia PEN en el 7 por ciento de Peptostreptococcus spp., a MET en 4 de 5 bacilos no esporulados y sensibilidad al resto de los antibióticos

Estudio multicéntrico de la sensibilidad de bacterias anaerobias en la Argentina / Multicentric study of anaerobic bacteria susceptibility in Argentina

Se determinó la actividad de ampicilina (AMP), ampicilina-sulbactama (AMS), penicilina (PEN), piperacilina (PIP), imipenem (IMI), cefoxitina (CXT), ceftizoxima (CFZ), clindamicina (CLI), cloranfenicol (CLO) y metronidazol (MET) frente a 106 cepas de bacterias anaerobias aisladas de muestras clínicas en seis centros asistenciales del país por un método de dilución en agar. Todos los microorganismos gramnegativos fueron sensibles a AMS, CLO, IMI y MET. Se encontraron 5/7 Bacteroides spp., 2/6 bacilos gram negativos pigmentados y 1/4 Fusobacterium spp. resistentes a AMP. Los Bacteroides del grupo fragilis fueron altamente resistentes a AMP y la especie Bacteroides fragilis fue más sensible a PIP, CXT, CFZ y CLI que las otras especies del grupo (5 por ciento vs. 21 por ciento, 5 por ciento vs. 7 por ciento, 8 por ciento vs. 14 por ciento y 2,5 por ciento vs. 14 por ciento respectivamente). Entre los organismos gram positivos se encontró resistencia PEN en el 7 por ciento de Peptostreptococcus spp., a MET en 4 de 5 bacilos no esporulados y sensibilidad al resto de los antibióticos (AU)

Natural distribution of 5 bacteria associated with periodontal disease.

The purpose of this study was to determine the prevalence and distribution of 5 bacterial pathogens in subgingival plaque, their relationship with each other and probing depth. Plaque was collected from 6905 sites in 938 subjects. A bacterial concentration fluorescence immunoassay and bacterial specific monoclonal antibodies were used to determine the presence and level of P. gingivalis (Pg), A. actinomycetemcomitans (Aa), P. intermedia (Pi), E. corrodens (Ec) and F. nucleatum (Fn) in each plaque sample. The prevalence in subjects was lowest for Pg (32%) and highest for Ec (49%). The site-based frequency distribution of these bacterial species ranged from 10.3% for Pg to 18.7% for Ec. Pi and Ec were the bacterial combination most often found together in a subject (27.2%). While 64.0% of the sites were without any of the 5 bacterial species evaluated, 20.2% had only 1 of the 5 bacterial species evaluated. The remaining 15.8% of sites had at least 2 bacteria species present. There was a general linear association of the detection level of bacterial species and probing depth. The odds ratios were 3.9 (Pg), 3.0 (Aa), 4.0 (Pi), 2.7 (Ec) and 2.8 (Fn) of finding high levels of these bacterial pathogens at > 5 mm probing depth (p < or = 0.01). Mean probing depth at molar sites without a specific bacteria was greater (p < or = 0.01) in subjects with a specific bacterium compared to molar sites in subjects without the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of periodontal disease in a health maintenance organization and comparisons to the national survey of oral health.

The purposes of this study were to: 1) characterize the demographics, oral health behavior, and periodontal status of a health maintenance organization sample; 2) investigate the relationship between the location of posterior proximal measurement sites and prevalence estimates for periodontal disease; and 3) compare the prevalence of persons with pockets > or = 4 mm in the present sample to the 1985 NIDR Survey of Oral Health. The sample consisted of 1,090 adults attending a large health maintenance organization. All proximal sites in one randomly selected posterior dental sextant were examined for probing depth using a constant force probe. Demographic, medical, and behavioral factors were determined by questionnaire. Results indicated that the sample consisted primarily of medically and periodontally-healthy middle-aged adults with good oral hygiene habits. Overall, the mean probing depth was 2.95 mm with 10.1% of sites/subject > or = 4 mm. A larger percent of subjects had probing depths with pockets > or = 4 mm at lingual proximal sites than buccal proximal sites. Prevalence of subjects with pockets > or = 4 mm at mesio-buccal sites in the present study was similar to NIDR Region III data (15.3% vs. 17.4% respectively). However, when data from all posterior sites were included, the overall prevalence rate in the present sample increased to 36.8%. These findings indicate that disease prevalence is dependent on the location of surfaces measured and conservatively indicate that NIDR survey data may have underestimated the prevalence of persons with periodontal pockets > or = 4 mm by at least 20%.