Effects of the Clarion Electrode Positioning System on auditory thresholds and comfortable loudness levels in pediatric patients with cochlear implants.

OBJECTIVE: To evaluate the effects of using the Electrode Positioning System on psychophysical auditory thresholds, most comfortable loudness levels, and electric auditory brainstem response (EABR) thresholds in children with the Clarion version 1.2 cochlear implant. DESIGN: Retrospective analysis. SETTING: Academic tertiary care center. PATIENTS AND METHODS: Clinical records of a series of 25 children who received the Clarion version 1.2 cochlear implant at the University of Minnesota, Minneapolis, between January 1997 and August 1999 were examined. Measures evaluated were psychophysical thresholds (T-levels) and most comfortable loudness levels (M-levels) obtained at the 3-month posthookup audiologic evaluation and EABR thresholds obtained during implant surgery. Relevant threshold measures were available for 24 patients, 11 of whom had received the Clarion spiral electrode and electrode positioner (EP group) and 13 of whom had received the spiral electrode without positioner (non-EP group). The 3 measures (T-levels, M-levels, and EABR thresholds) were compared across groups. In addition, EABR thresholds were compared with T-levels and M-levels within groups. RESULTS: Mean T-levels and M-levels were significantly lower for the EP group than for the non-EP group, and interpatient variability for these measures was considerably smaller in the EP group. Electric auditory brainstem response thresholds were not significantly different for EP vs non-EP patients; however, EABR data were available for only a few non-EP patients. CONCLUSIONS: Use of the electrode positioner results in lower T-levels and M-levels in children with the Clarion version 1.2 cochlear implant, consistent with results of previous studies in adults, and reduces across-patient variability for these measures. It is unclear from the present data whether use of the electrode positioner systematically reduces intraoperative EABR thresholds.

Lightening the lead load in children.

More than 4 percent of preschool-aged children in the United States have blood lead levels above 10 microg per dL (0.50 pmol per L), and these levels have been associated with a decline in IQ. The Centers for Disease Control and Prevention advocates the use of a screening questionnaire to identify lead exposure or toxicity in all children. Primary prevention through the removal of lead from gasoline and paint has led to a reduction of blood lead levels in children. Secondary prevention through paint hazard remediation is effective in homes that have a high lead burden. Children with lead levels of 45 to 69 microg per dL (2.15 to 3.35 pmol per L) should receive chelation therapy using succimer (DMSA) or edetate calcium disodium (CaNa2EDTA). Use of both CaNa2EDTA and dimercaprol (BAL in oil) is indicated in children with blood lead levels higher than 70 microg per dL (3.40 micromol per L). Current treatment recommendations are based on the reduction of blood lead levels, which may not represent a significant overall reduction of the lead burden. Clinical trials of existing agents are needed to determine patient-oriented outcomes, such as the effect on IQ.

Measurements of loudness growth in 1/2-octave bands for children and adults with normal hearing.

The loudness growth in 1/2-octave bands (LGOB) procedure has been shown previously to provide valid estimates of loudness growth for adults with normal hearing and those with hearing loss (Allen, Hall, & Jeng, 1990), and it has been widely incorporated into fitting strategies for adult hearing aid users by a hearing aid manufacturer. Here, we applied a simple modification of LGOB to children and adults with normal hearing and then compared the loudness growth functions (as obtained from end-point data) between the two age groups. In addition, reliability data obtained within a single session and between test sessions were compared between the two groups. Large differences were observed in the means between the two groups for the lower boundary values, the upper boundary values, and the range between boundaries both within and across all frequencies. The data obtained from children also had greater variance than the adult data. In addition, there was more variability in the data across test sessions for children. Many test-retest differences for children exceeded 10 dB. Adult test-retest differences were generally less than 10 dB. Although the LGOB with the modifications used in this study may be used to measure loudness growth in children, its poor reliability with this age group may limit its clinical use for children with hearing loss. Additional work is needed to explore whether loudness growth measures can be adapted successfully to children and whether these measures contribute worthwhile information for fitting hearing aids to children.

Addressing spiritual concerns of patients: family physicians' attitudes and practices.

BACKGROUND: Our goals were to assess family physicians' spiritual well-being, identify their perceived barriers to discussing spiritual issues with patients, and determine how often they have these discussions. METHODS: We mailed a questionnaire to 231 Missouri family physicians (80 residents, 43 faculty, and 108 community physicians). The questionnaire included the Ellison Spiritual Well-being Scale (ESWS), as well as questions about physicians' attitudes toward spirituality and the barriers to and frequency of discussions of spiritual issues with patients. RESULTS: The response rate was 74%. The mean ESWS score indicated that the physician respondents had a high level of spiritual well-being. Nearly all respondents (96%) considered spiritual well-being an important health component, 86% supported referral of hospitalized patients with spiritual questions to chaplains, and 58% believed physicians should address patients' spiritual concerns. Fear of dying was the spiritual issue most commonly discussed, and less than 20% of physicians reported discussing other spiritual topics in more than 10% of patient encounters. Barriers to addressing spiritual issues included lack of time (71%), inadequate training for taking spiritual histories (59%), and difficulty identifying patients who want to discuss spiritual issues (56%). CONCLUSIONS: Family physicians in this survey had high spiritual well-being scores. Most believed spiritual well-being is an important factor in health. Despite this belief, however, most reported infrequent discussions of spiritual issues with patients and infrequent referrals of hospitalized patients to chaplains. Lack of time and training were key barriers to spiritual assessment.

Evidence for the involvement of Glu-355 in the catalytic action of human beta-hexosaminidase B.

In a previous study the photoactivable affinity probe, 3-azi-1-[([6-3H]2-acetamido-2-deoxy-1-beta-D-galactopyranosyl)thio ]-b utane, was used to identify the active site of beta-hexosaminidase B, a beta-subunit dimer (Liessem, B., Glombitza, G. J., Knoll, F., Lehmann, J., Kellermann, J., Lottspeich, F., and Sandhoff, K. (1995) J. Biol. Chem. 270, 23693-23699). The probe predominately labeled Glu-355, a highly conserved residue among hexosaminidases. To determine if Glu-355 has a role in catalysis, beta-subunit mutants were prepared with the Glu-355 codon altered to either Ala, Gln, Asp, or Trp. After expression of mutant proteins using recombinant baculovirus, the enzyme activity associated with the beta-subunits was found to be reduced to background levels. Although catalytic activity was lost, the mutations did not otherwise affect the folding or assembly of the subunits. The mutant beta-subunits could be isolated using substrate affinity chromatography, indicating they contained intact substrate binding sites. As shown by cross-linking with disuccinimidyl suberate, the mutant beta-subunits were properly assembled. They could also participate in the formation of functional beta-hexosaminidase A activity as indicated by activator-dependent GM2 ganglioside degradation activity produced by co-expression of the mutant beta-subunits with the alpha-subunit. Finally, the mutant subunits showed normal lysosomal processing in COS-1 cells, demonstrating that a transport-competent protein conformation had been attained. Collectively the results provide strong support for the intimate involvement of Glu-355 in beta-hexosaminidase B-mediated catalysis.

Mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine against herpesviruses.

The activity, metabolism, and mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (H2G) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and varicella-zoster virus (VZV) were studied. Compared to acyclovir (ACV), H2G has superior activity against VZV (50% inhibitory concentration of 2.3 microM) and Epstein-Barr virus (50% inhibitory concentration of 0.9 microM), comparable activity against HSV-1, and weaker activity against HSV-2. The antiviral effect on HSV-1 showed persistence after removal of compound. H2G was metabolized to its mono-, di- and triphosphate derivatives in virus-infected cells, with H2G-triphosphate being the predominant product. Only small amounts of H2G-triphosphate were detected in uninfected cells (1 to 10 pmol/10(6) cells), whereas the level in HSV-1-infected cells reached 1,900 pmol/10(6) cells. H2G was a substrate for all three viral thymidine kinases and could also be phosphorylated by mitochondrial deoxyguanosine kinase. The intracellular half-life of H2G-triphosphate varied in uninfected (2.5 h) and infected (HSV-1, 14 h; VZV, 3.7 h) cells but was always longer than the half-life of ACV-triphosphate (1 to 2 h). H2G-triphosphate inhibited HSV-1, HSV-2, and VZV DNA polymerases competitively with dGTP (Ki of 2.8, 2.2, and 0.3 microM, respectively) but could not replace dGTP as a substrate in a polymerase assay. H2G was not an obligate chain terminator but would only support limited DNA chain extension. Only very small amounts of radioactivity, which were too low to be identified by high-performance liquid chromatography analysis of the digested DNA, could be detected in purified DNA from uninfected cells incubated with [3H]H2G. Thus, H2G acts as an anti-herpesvirus agent, particularly potent against VZV, by formation of high concentrations of relatively stable H2G-triphosphate, which is a potent inhibitor of the viral DNA polymerases.

Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale).

The dried rhizomes of Indonesian ginger, Zingiber officinale, were investigated for antirhinoviral activity in the plaque reduction test. Fractionation by solvent extraction, solvent partition, and repeated chromatography guided by bioassay, allowed the isolation of several sesquiterpenes with antirhinoviral activity. The most active of these was beta-sesquiphellandrene [2] with an IC50 of 0.44 microM vs. rhinovirus IB in vitro.

Coagulopathy screening in children with heparinized central venous catheters.

OBJECTIVE: To develop a method of screening for coagulopathy using blood drawn through heparinized central venous catheters. METHODS: Prothrombin time (PT) and activated partial thromboplastin time (APTT) were determined in paired blood samples with and without the addition of protamine, using an automated photo-optical method. A concentration of 4 micrograms/mL of citrated whole blood was chosen, based on preliminary experiments. This is sufficient to neutralize the expected heparin contamination in samples drawn through heparinized catheters while causing only a slight prolongation in APTT (due to the anticoagulant effect of protamine). Seventeen paired samples were drawn by venipuncture in patients without known coagulopathy. Twenty-five samples were drawn through heparinized central venous catheters. The first 5 mL of blood drawn from a catheter was discarded to avoid gross heparin contamination. Four samples from patients with coagulopathy were also analyzed with and without the addition of 2.5 micrograms/mL of heparin. RESULTS: Protamine increased PT by 9.0 +/- 0.8% and APTT by 9.0 +/- 3.4% (mean +/- SD) in the samples drawn by venipuncture. For samples drawn through heparinized catheters, 52% had a prolonged APTT, 44% a prolonged PT, and 68% had at least one prolonged test. With the addition of protamine, and after correction for the 9% mean increase in PT and APTT, 4% of samples had a prolonged APTT, 12% had a prolonged PT, and 16% had at least one prolonged test (P = .00006, .014, and .0001). All four samples from patients with coagulopathy were correctly identified as abnormal after the addition of protamine, with or without added heparin. CONCLUSIONS: A protamine-supplemented APTT test on blood drawn through a heparinized catheter may be an adequate screening test for coagulopathy. This procedure reduces discomfort in patients with an indwelling catheter by avoiding venipuncture.

Colour-coded duplex ultrasonography in the selection of patients for endovascular surgery.

Endovascular surgery using angioplasty or atherectomy may potentially relieve the symptoms of claudicants with minimal morbidity, but results are best when short stenoses are treated. In this study, colour-coded duplex ultrasonography has been compared with angiography. In aortoiliac segments duplex examination had a sensitivity of 88 per cent and a specificity of 100 per cent; in femoropopliteal disease the sensitivity was 100 per cent and duplex scanning identified more disease than angiography. Subsequently, 73 symptomatic limbs with femoropopliteal disease were scanned to assess their suitability for endovascular surgery. Of these limbs, 27 (37 per cent) had suitable lesions and the remaining 46 (63 per cent) were spared angiography. Colour-coded duplex ultrasonography can reliably be used to select patients for endovascular surgery.

Prevalence, progression and natural history of asymptomatic carotid stenosis: is there a place for carotid endarterectomy?

The purpose of this study was to determine the prevalence, progression and prognosis of asymptomatic carotid artery stenosis in a population of 1198 patients with peripheral arterial disease (n = 986) or aortic aneurysm (n = 212), mean age 67.7 (S.D. = 10.0) years. Patients were recruited from 1985 to 1989 with annual assessment of carotid artery stenosis of over 50% using Doppler peak frequency analysis. Patients were followed up annually until 1990 or their first event, transient ischaemic attack (TIA), amaurosis fugax (AFx), stroke without antecedent TIA, or death (mean follow up 20 months). Life tables were used to determine risk of events in different patient groups. Only 164 (13.7%) patients had a stenosis of over 50% in either of the common or internal carotid arteries, disease was bilateral in 33 (2.8%) patients. A total of 33 patients (2.8%) had over 80% stenosis in common or internal carotid arteries. During follow up 37 (3.1%) patients developed a stenosis greater than 50%. Only 27 (2.3%) patients developed a stroke, 11 of which were fatal. A further 33 (2.8%) suffered a TIA or AFx and a total of 155 patients died during follow up. The total neurological event rate (TIA, AFx and stroke) was significantly associated with the presence of over 50% stenosis, [relative risk (RR) = 2.98, 95% confidence interval (95% C.I.) 1.68-5.29, p less than 0.001] and carotid bruit (RR = 1.16, 95% C.I. 1.23-3.81, p = 0.010). Although risk of stroke was higher in patients with a 50% stenosis, this failed to achieve statistical significance (RR = 1.78, 95% C.I. 0.66-4.80, p = 0.275).(ABSTRACT TRUNCATED AT 250 WORDS)

Management of asymptomatic carotid bruit.

One hundred forty-nine consecutive patients who had peripheral arterial disease (PAD) with clinically audible asymptomatic bruits were studied. Sixty-two of these patients were age- and sex-matched with 62 PAD patients in whom no bruits were detected. The PAD was demonstrated by angiography or by the 1-minute exercise test. Clinical assessment was performed every 6 months and oculoplethysmography and carotid phonoangiography (OPG/CPA) were performed every year. Angiography and reconstructive surgery were performed only if symptoms of transient ischemic attack (TIA) or stroke occurred. Life-table analysis revealed that over a 5.5-year follow-up, 32% of 211 PAD patients were expected to die. In the control study 45% of bruit patients and 32% of control patients were expected to die (no significant difference). Myocardial infarction accounted for 59% of deaths in the bruit group compared with 28% in the control group (no significant difference). TIA occurred more commonly in the bruit group (26.5%) than in the controls (6%) (p less than 0.02). However, stroke without warning occurred in 9% of bruit patients compared with 8% of controls (no significant difference). It is concluded that for asymptomatic carotid bruit it is safe to wait for the onset of symptoms before angiography and corrective reconstructive surgery.