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Biomedical subjects

H W Francis

Publications and source records attributed to H W Francis.

At least 19 recordsLinked to original sources

Squamous cell carcinoma of the temporal bone: a radiographic-pathologic correlation.

OBJECTIVE: To assess the utility of a previously proposed staging system for patients with primary squamous cell carcinoma of the temporal bone. METHODS: Retrospective chart review of 15 patients treated for squamous cell carcinoma of the temporal bone over a 13-year period at an academic tertiary referral center. A review of the medical and surgical records, radiographic studies, and surgical pathology reports allowed for an evaluation of the University of Pittsburgh staging system. Outcome analysis was performed on 13 patients with more than 24 months of follow-up. RESULTS: Radiographic and surgical pathology staging according to the University of Pittsburgh staging system correlated in 11 (73%) of 15 cases. The radiographic staging system was more accurate for larger (T3/T4) tumors than for smaller (T1/T2) tumors (83% vs 67%). When compared with patients with no evidence of disease, nonsurvivors were more likely to present with otalgia (67% vs 43%), facial nerve paralysis (33% vs 0%), and T3/T4 tumors (100% vs 14%). CONCLUSIONS: Pathologic staging by the University of Pittsburgh staging system closely correlates with patient outcome and is more sensitive than preoperative radiographic staging. Prognosis in squamous cell carcinoma of the temporal bone is largely determined by the extent of local disease at the time of presentation.

Aged↗

Cost-utility analysis of the cochlear implant in children.

CONTEXT: Barriers to the use of cochlear implants in children with profound deafness include device costs, difficulty assessing benefit, and lack of data to compare the implant with other medical interventions. OBJECTIVE: To determine the quality of life and cost consequences for deaf children who receive a cochlear implant. DESIGN: Cost-utility analysis using preintervention, postintervention, and cross-sectional surveys conducted from July 1998 to May 2000. SETTING: Hearing clinic at a US academic medical center. PARTICIPANTS: Parents of 78 profoundly deaf children (average age, 7.5 years) who received cochlear implants. MAIN OUTCOME MEASURES: Direct and total cost to society per quality-adjusted life-year (QALY) using the time-trade-off (TTO), visual analog scale (VAS), and Health Utilities Index-Mark III (HUI), discounting costs and benefits 3% annually. Parents rated their child's health state at the time of the survey and immediately before and 1 year before implantation. RESULTS: Recipients had an average of 1.9 years of implant use. Mean VAS scores increased by 0. 27, from 0.59 before implantation to 0.86 at survey. In a subset of participants, TTO scores increased by 0.22, from 0.75 to 0.97 (n = 40) and HUI scores increased by 0.39, from 0.25 to 0.64 (n = 22). Quality-of-life scores were no different 1 year before and immediately before implantation. Discounted direct costs were $60,228, yielding $9,029 per QALY using the TTO, $7,500 per QALY using the VAS, and $5,197 per QALY using the HUI. Including indirect costs such as reduced educational expenses, the cochlear implant provided a savings of $53,198 per child. CONCLUSIONS: Cochlear implants in profoundly deaf children have a positive effect on quality of life at reasonable direct costs and appear to result in a net savings to society. JAMA. 2000;284:850-856

Child↗

Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons.

When cochlear pathology impairs the afferent innervation of the ventral cochlear nucleus (VCN), electrical responses of the auditory brainstem are altered and changes in cell and synaptic morphology are observed. However, the impact of deafferentation on the electrical properties of cells in the VCN is unknown. We examined the electrical properties of single neurons in the anterior and posterior VCN following bilateral cochlear removal in young rats. In control animals, two populations of cells were distinguished: those with a linear subthreshold current-voltage relationship and repetitive firing of action potentials with regular interspike intervals (type I), and those with rectifying subthreshold current-voltage relationships and phasic firing of 1-3 action potentials (type II). Measures of action potential shape further distinguished these two groups. Two weeks following cochlear removal, both electrical response patterns were still seen. Type I cells showed a higher input resistance. Deafferented single-spiking type II cells were slightly more depolarized, had smaller action potentials, smaller afterhyperpolarizations and shorter membrane time constants, whereas multiple-spiking type II cells were apparently unaffected. These changes in the electrical properties of VCN neurons following cochlear injury may adversely affect central processing of sounds presented acoustically or electrically by prostheses.

Afferent Pathways↗

Immune-mediated inner ear disease.

Immune-mediated inner ear disease (IMIED) is a syndrome that includes the subacute onset of sensorineural hearing loss, often accompanied by vertigo and tinnitus. This constellation of symptoms may occur as a primary disorder in which no other organ involvement is evident, or it may complicate certain systemic conditions, including Wegener's granulomatosis, Cogan's syndrome, polyarteritis nodosa, and systemic lupus erythematosus. The precise disease mechanisms remain undefined, largely because of the difficulty obtaining relevant tissue specimens in untreated patients. However, if treated promptly with aggressive immunosuppression, the devastating sequelae of IMIED may be avoided. In this article, we review the pathophysiology, clinical evaluation, diagnostic testing, and therapy of IMIED.

Diagnosis, Differential↗

Trends in educational placement and cost-benefit considerations in children with cochlear implants.

OBJECTIVES: To study the effect of cochlear implantation on the use of educational resources by profoundly hearing-impaired children and to determine trends in educational cost vs benefit. DESIGN: Retrospective study and cost-benefit analysis. SETTING: Outpatient pediatric cochlear implant program in an academic institution (The Listening Center at Johns Hopkins University School of Medicine, Baltimore, Md), in collaboration with public schools in Maryland and surrounding states. PATIENTS OR OTHER PARTICIPANTS: School-aged children with profound prelingual hearing impairment without other clearly defined disabilities. Thirty-five children with multiple-channel cochlear prostheses and a comparison group of 10 children without implants from 'total communication' programs in the Maryland public school system. INTERVENTIONS: Multiple-channel cochlear implantation and at least 1 year of a systematic auditory skill development program at the Listening Center, compared with standard educational management of children with conventional amplification. MAIN OUTCOME MEASURES: Classroom placement and number of hours of special educational support used. RESULTS: A correlation was observed between the length of cochlear implant experience and the rate of full-time placement in mainstream classrooms (r = 0.10; P= .04). There was also a negative correlation between the length of implant experience and the number of hours of special educational support used by fully mainstreamed children (Pearson product moment correlation = -0.10; P = .03). Children with greater than 2 years of implant experience were mainstreamed at twice the rate or more of age-matched children with profound hearing loss who did not have implants. They were also placed less frequently in self-contained classrooms and used fewer hours of special education support. A cost-benefit analysis based on conservative estimates of educational expenses from kindergarten to 12th grade shows a cost savings of cochlear implantation and appropriate auditory (re)habilitation that ranges from $30000 to $200000. CONCLUSIONS: Cochlear implantation accompanied by aural (re)habilitation increases access to acoustic information of spoken language, leading to higher rates of mainstream placement in schools and lower dependence on special education support services. The cost savings that results from a decrease in the use of support services indicates an educational cost benefit of cochlear implant (re)habilitation for many children.

Adolescent↗

An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host.

OBJECTIVE: To examine the pathogenesis of fulminant invasive fungal rhinosinusitis to determine factors that may affect patient survival. METHODS: Retrospective chart review of 25 patients treated for invasive fungal rhinosinusitis over a 10-year period at an academic tertiary referral center. Evaluation of the medical and surgical records, radiographic studies, surgical pathology specimens, and culture results allowed for a multifactorial comparison between survivors and nonsurvivors. Survivors were patients who left the hospital with the invasive fungal disease stable or cured. RESULTS: Fungal invasion often occurs within the nasal cavity (92% of patients), most commonly at the middle turbinate (62% of patients receiving biopsy). Survivors had complete surgical resection more often than nonsurvivors (90% vs 0%), and were more likely to respond to granulocyte colony-stimulating factor than nonsurvivors (100% vs 0% of those treated). CONCLUSIONS: Rigid nasal endoscopy with frozen section biopsy of suspicious nasal lesions and high-incidence areas (ie, middle turbinate) allows for the timely diagnosis of invasive fungal rhinosinusitis. Survival improves if the disease is limited to the nasal or sinus cavities, which may represent an earlier stage of disease. Favorable prognostic signs include the ability to achieve a complete surgical resection and a positive response to granulocyte colony-stimulating factor in the neutropenic patient.

Adolescent↗

A model of educational resource use by children with cochlear implants.

We have tracked patterns of use of educational and rehabilitative resources as part of an initial assessment of cost-benefit ratios of cochlear implants in children. Forty-two children with cochlear implants in the Listening Center at Johns Hopkins program of aural rehabilitation have served as our study cohort to develop the measures to be assessed. An educational resource matrix stratifies school setting (residential vs special education vs non-specialized "mainstream" setting) and levels of rehabilitative support (speech and language therapy and interpreter use) to map past and current use of these services. Initial cost-benefit projections based on observed advancement toward educational independence in the educational resource matrix indicate an extremely favorable net present value of the implant (cost savings minus cost). These cost-benefit projections will need to be supplemented with measures of the impact on quality of life and future educational and vocational options to determine the overall cost-effectiveness of cochlear implants in children.

Baltimore↗

Association of heterotopic neuroglial tissue with an arachnoid cyst in the internal auditory canal.

An arachnoid cyst arising within the internal auditory canal, or within the cerebellopontine angle and subsequently extending into the internal meatus and enlarging it, is a rare occurrence. Nevertheless, the neurootologist and the neurosurgeon have an interest in its existence because its clinical manifestations are identical with the ones produced by a schwannoma, involving overwhelmingly the cochleovestibular nerve in that region. An equally rare observation in that location is the presence of ectopic neuroglial tissue. The two can occur independently or in combination. Examples of such lesions are presented, and their possible pathogenesis is discussed.

Journal Article↗

Disappearance kinetics of solutes from synovial fluid after intra-articular injection.

1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions.

Acetaminophen↗

Patterns of innervation of outer hair cells in a chimpanzee: I. Afferent and reciprocal synapses.

Three varieties of synaptic specialization, afferent, efferent, and reciprocal, have been demonstrated at the base of outer hair cells of one chimpanzee. The purpose of the present study was to investigate the innervation density of afferent and reciprocal synapses in the three rows and three turns of the organ of Corti. The data presented is based on light and electron microscopy from one aged chimpanzee using serial section electron microscopy. Afferent fibers make contact with outer hair cells as either terminal swellings or en passant contacts. In addition to membrane specialization, presynaptic bodles were present at the majority of afferent synapses. The mean innervation density of afferent endings was highest in the middle turn. Reciprocal endings were found on 74% of all outer hair cells. The average number of reciprocal endings increased from the base to apex and, except in the apical turn, from the first to third row of outer hair cells. On the basis of morphological criteria, endings with a reciprocal synapses were more similar to afferent than to efferent endings.

Animals↗

Patterns of innervation of outer hair cells in a chimpanzee: II. Efferent endings.

A morphometric analysis of the efferent innervation of the outer hair cells in the organ of Corti of one chimpanzee was performed. There was a wide variability in the size of efferent endings which ranged from approximately 0.1 to 4.5 microns 3 in volume. Based on the size distribution of endings, a volume of 1.0 microns 3 was chosen to divide efferent endings into two groups, 'large' and 'small'. The incidence of large efferent fibers decreased from base to apex and from the first to third row of each turn, whereas the incidence of small efferents increased from base to apex and from the first to third row in each turn. This data was interpreted to suggest that at least two types of efferent endings may exist at the base of outer hair cells of the organ of Corti in the chimpanzee.

Animals↗

Enantiospecific gas chromatographic-mass spectrometric procedure for the determination of ketoprofen and ibuprofen in synovial fluid and plasma: application to protein binding studies.

A method for the enantiospecific quantitation of two commonly prescribed non-steroidal anti-inflammatory drugs (ketoprofen and ibuprofen) is described. The method involves formation of a mixed anhydride of the drug with ethylchloroformate and subsequent conversion to an amide by reaction with optically active amphetamine. The subsequently formed diastereomers are separated by gas chromatography-mass spectrometry using selected-ion monitoring. The assay is capable of quantifying ketoprofen (2 ng/ml) and ibuprofen (3 ng/ml) enantiomers from a 200-microliters sample of synovial fluid or plasma and is particularly suitable for protein binding studies.

Gas Chromatography-Mass Spectrometry↗

Dosage prescribing and plasma oxipurinol levels in patients receiving allopurinol therapy.

This study examined dosage prescribing patterns and steady-state oxipurinol plasma concentrations in 66 patients receiving chronic allopurinol therapy. Most patients (65%) were taking 300 mg allopurinol daily, although renal impairment was common. Using published guidelines, it was estimated that 35% of patients were receiving excessive dosages of allopurinol. Consequently, the plasma oxipurinol concentrations were often very high (mean (SD) was 156 (109) mumol.l-1). Accumulation of oxipurinol was inversely related to renal function. Plasma concentrations of oxipurinol and urate were not significantly related. However, most patients with oxipurinol concentrations of up to 100 mumol.l-1 had urate concentrations within the normal reference range.

Aged↗

Salicylate pharmacokinetics in patients with rheumatoid arthritis.

1. The pharmacokinetics of salicylic acid (SA) and its major metabolite salicyluric acid (SU) were studied in nine patients with rheumatoid arthritis following a 900 mg oral dose of acetylsalicylic acid and during 6 weeks of chronic administration of enteric coated aspirin (3,900 mg day). Response to therapy was also monitored. 2. The various pharmacokinetic parameters determined in the study were similar to those observed in other single dose salicylate studies amongst healthy volunteers but were not predictive of salicylate concentration in the chronic dose study. 3. Plasma concentrations of SA (total and unbound) were found to decline significantly over the 6 weeks and plasma SU concentrations increased. 4. During the chronic dosing study, there was a significant increase in the Vmax (total and unbound) for the formation of SU, whilst the Km and SU clearance remained constant. Also, the elimination rate constant (k) for salicylate was not significantly affected. 5. Therapeutic response to salicylate therapy was not significantly affected by the decline in SA concentrations.

Aged↗