Biomedical subjects

D M Mills

Publications and source records attributed to D M Mills.

At least 19 recordsLinked to original sources

PubMed1999

Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori.

Helicobacter pylori, one of the most common bacterial pathogens of humans, colonizes the gastric mucosa, where it appears to persist throughout the host's life unless the patient is treated. Colonization induces chronic gastric inflammation which can progress to a variety of diseases, ranging in severity from superficial gastritis and peptic ulcer to gastric cancer and mucosal-associated lymphoma. Strain-specific genetic diversity has been proposed to be involved in the organism's ability to cause different diseases or even be beneficial to the infected host and to participate in the lifelong chronicity of infection. Here we compare the complete genomic sequences of two unrelated H. pylori isolates. This is, to our knowledge, the first such genomic comparison. H. pylori was believed to exhibit a large degree of genomic and allelic diversity, but we find that the overall genomic organization, gene order and predicted proteomes (sets of proteins encoded by the genomes) of the two strains are quite similar. Between 6 to 7% of the genes are specific to each strain, with almost half of these genes being clustered in a single hypervariable region.

Duodenal Ulcer↗

PubMed1999

Cochlear implant performance after reimplantation: a multicenter study.

OBJECTIVE: This study compares auditory performance between original and replacement cochlear implants. STUDY DESIGN AND SETTING: Data from 18 U.S. cochlear implant programs were obtained by retrospective chart review. Patients received and returned subjective questionnaires. PATIENTS: Twenty-eight adults with once-functioning Nucleus 22 cochlear implants that failed received replacement Nucleus 22 cochlear implants in the same ears. MAIN OUTCOME MEASURES: Objective measures included sentence (CID Everyday Sentences or Iowa Sentences) and monosyllabic word (NU-6 Words or CNC Words) speech discrimination scores. Patients also rated and compared performance using subjective scales. RESULTS: Thirty-seven percent of patients had significantly higher sentence or word scores with their replacement cochlear implants than with their original implants, 26% had no significant change, and 37% had significantly poorer scores. Subjectively, 57% of patients reported that the performance of their replacement device was better or the same and 43% reported that it was poorer. There was no correlation between performance with the replacement cochlear implant and cause of the original device failure, duration of original device use before failure, surgical complications with either implantation, changes in electrode insertion depths, or preoperative variables, such as age, etiology, or duration of deafness. CONCLUSIONS: Speech recognition ability with a replacement cochlear implant may significantly increase or decrease from that with the original implant. Experienced cochlear implant patients facing reimplantation must be counseled regarding the possibility of differences in sound quality and speech recognition performance with their replacement device.

Adult↗

PubMed1998

Development of the base of the cochlea: place code shift in the gerbil.

Distortion product otoacoustic emission measurements were made at 1/12 octave intervals before and after the injection of furosemide in gerbils aged 15 days after birth to adult, in order to obtain estimates of cochlear amplifier gain as a function of stimulus frequency. The frequency at which the gains went sharply to zero, defined as the 'base cutoff frequency', increased from about 20 kHz to over 50 kHz during development. This increase provides further confirmation of the hypothesis that the place code changes during development in the basal part of the cochlea. If the measured base cutoff frequency is identified with the characteristic frequency at the basal end of the cochlea, as defined by electrophysiological measures, then these emission data can be used to generate a frequency-place map as a function of age. The derived place code shift is consistent with published electrophysiological measures, and can be used to extend these measures. Near the base cutoff frequency, the observed cochlear amplifier gain typically dropped sharply from a relative maximum to zero, over a distance of about a half octave. Specifically, this distance appeared to exhibit a curvilinear variation with age, reaching a maximum of 3/4 of an octave at 19-21 days. After transforming from frequency to place using the map derived from emissions, however, the distance between the extreme base and the place associated with the peak gain decreased monotonically from about 1.2 mm at age 15-19 days to 0.6 mm at maturity. This distance is assumed to be characteristic of the length of the active amplification zone for the cochlear amplifier in the base region. Over the same time period, there was approximately a doubling of the rate of amplification with distance from the base, so that the cochlear amplifier gain at the peak actually changed very little from 15 days to adult.

Acoustic Stimulation↗

PubMed1998

Interpretation of distortion product otoacoustic emission measurements. II. Estimating tuning characteristics using three stimulus tones.

The simple model introduced in Part I [J. Acoust. Soc. Am. 102, 413-429 (1997)] is used to simulate the response of the cochlea to three stimulus tones. The focus is on "emission suppression tuning curves" constructed using a third tone to suppress the cubic distortion tone emission (CDT, 2f1-f2) generated by two primary tones at frequencies f1 and f2 (intensities L1 and L2). A criterion decrease (here, 5 dB) of the CDT emission amplitude defines the 2f1-f2 emission suppression tuning curve. Applying traditional tuning curve measures to emission suppression tuning curves appears ineffective in determining the underlying cochlear amplifier characteristics. However, it is shown that there are three characteristics of emission suppression tuning curves which are particularly useful: (1) the "f2 threshold" which is the level of the third tone, L3, required for the criterion CDT amplitude decrease, under the condition that the third tone frequency, f3, is approximately equal to f2; (2) the "shoulder threshold" similarly defined for f3 << f2; and (3) the "tuning width," w40. The tuning width is defined to be the distance (in octaves) from the frequency f2 to the upper f3 frequency for which there is a criterion CDT decrease, in this case using the L3 level which is 40 dB above the f2 threshold. Model calculations appropriate to gerbils show that these measures are most accurately related to the underlying cochlear amplifier characteristics for parameters where the primary stimulus amplitudes satisfy L1/L2 > 20 dB and for which L1 is 25 dB or more below the sharp "notch" seen in the two tone input-output function. In this parameter region, the cochlear amplifier characteristics are related to measured quantities by the relationships wr approximately equal to w40 and Ga approximately equal to TE + w40gp. Here, Ga is the gain (dB) of the cochlear amplifier, defined as the total increase in cochlear response over the passive response, wr is the distance (octaves) over which the active cochlear response rises to a maximum, and gp is the passive increase (dB/octave) of the traveling wave along the basilar membrane. The measured quantities are TE, the difference (dB) between the shoulder threshold and the f2 threshold, and the tuning width, w40 (octaves), defined above. Model predictions are confirmed by measurements in adult gerbils.

Acoustic Stimulation↗

PubMed1997

5- to 18-year follow-up study of cemented total knee arthroplasty for patients 55 years old or younger.

Seventy-two cemented total knee arthroplasties were performed on 52 patients who were 55 years old or younger. Results on 68 knees in 50 patients with an average follow-up period of 9.92 years are reported. The average age of the patients was 50.7 years (range, 30-55) at the time of surgery. The diagnosis was osteoarthritis in 37 knees, rheumatoid arthritis in 29 knees, and ankylosing spondylitis in 2 knees. The average preoperative Knee Society knee score was 23 and the average follow-up knee score was 97. All knees were rated as good or excellent for knee score. The average latest function score was 75 (preoperative, 36). Both knees in one patient required revision for loose components. This review demonstrates that cemented total knee arthroplasty in younger patients with osteoarthritis and rheumatoid arthritis can attain results comparable to the excellent results obtained in the older age groups.

Age Factors↗

PubMed1997

Development of distortion product emissions in the gerbil: "filter" response and signal delay.

Amplitude and phase responses of distortion product otoacoustic emissions as a function of stimulus frequency ratio were measured for frequencies between 2 and 48 kHz, in Mongolian gerbils (Meriones unguiculates) aged 15 to 30 days after birth. After baseline measurements, furosemide was administered to distinguish active from passive emissions. At all ages, structure in the form of multiple peaks was observed in the amplitude responses of specific odd-order emissions. This structure depended on the emission frequency, not the stimulus frequency ratio, and did not generally depend on the stimulus amplitude. Nor was it dependent on the functioning of the cochlear amplifier: At moderate stimulus levels, the observed emission distribution simply shifted to lower amplitudes when the cochlear amplifier was made temporarily dysfunctional by furosemide injection. The center frequencies and widths of the peaks in the amplitude response did not generally change with age, except that the relative amplitudes of the higher-frequency peaks were increased in younger animals. At 2 kHz, however, the distribution showed other evidence of maturation, with the frequency of maximum emission moving downward with age. The phase responses yielded estimates of the round trip signal (group or traveling wave) delay. At a given frequency, the active signal delay typically decreased substantially with increasing stimulus level. However, there was a rapid variation in delay as the stimulus level passed the normal active-passive crossover level. At stimulus levels measured relative to the active-passive crossover level, i.e., either 20 or 30 dB lower, the active signal delay decreased only slightly with age. Overall, both filter response and signal delay characteristics were found to be essentially mature near the onset of hearing.

Acoustic Stimulation↗

PubMed1997

Interpretation of distortion product otoacoustic emission measurements. I. Two stimulus tones.

The interpretation of common but poorly understood observed characteristics of distortion product emissions is assisted by the development of a simple model. This model essentially includes only saturation of the cochlear amplifier, with emissions arising naturally from the same nonlinear processes which cause the saturation. The model provides useful physical explanations of emission behaviour, particularly considered as a function of the stimulus intensities of the two primaries, i.e., behavior with fixed stimulus frequencies. It is assumed that emission generation consists of two main components which are always present in the total emission, but which most often have approximately opposite, i.e., canceling, phases. One component arises in a small region centered about the peak of the emission generation function, while the other arises from the region basal to this peak. At low stimulus levels with normal cochlear amplifier operation, the peak of the emission generation function is sharp, so the emission from the peak region dominates the total emission. This "peak" emission has typically been characterized as the "active" emission. At high stimulus levels where saturation is important, or at all levels when the gain of the cochlear amplifier is reduced, the summed "basal" component dominates the total emission. The characteristics of this basal emission are similar to, and continuous with, the characteristics of the truly "passive" emission, i.e., the emission observed when the cochlear amplifier gain is identically zero. Under circumstances when the emissions from the peak and basal components are approximately equal, there is seen a sharp "notch" characteristic of phase cancellation. The simple model produces emission distributions as a function of independent variation of the two stimulus amplitudes which are in good agreement with observation. It is shown that the furosemide assay provides a good estimate of cochlear amplifier gain when a correction factor of about 10 dB is added. However, when using two stimulus tones, neither absolute emission amplitudes, or emission input-output functions, or the furosemide assay can adequately distinguish between cases of moderate versus poor cochlear amplifier dysfunction when the cochlear amplifier gains are in the range from about half normal to zero.

Acoustic Stimulation↗

PubMed1996

Development of the cochlear amplifier.

The development of the cochlear amplifier was examined in gerbils aged 14 days after birth (dab) to adult, for stimulus frequencies from 1 to 48 kHz. Distortion product otoacoustic emissions (DPOAEs) were employed to determine the characteristics of active emissions associated with cochlear amplifier operation. DPOAEs were also used to determine the characteristics of "passive" emissions remaining when the cochlear amplifier operation was interrupted by acute furosmide intoxication. The input-output functions of the passive emissions, and of the active emissions at low stimulus levels, could be approximated by parallel straight lines. The horizontal distance between these parallel lines, i.e., the increase in stimulus level required to obtain a passive emission amplitude equal to the active emission, is an estimate of the gain of the cochlear amplifier. Further, the lowest stimulus level at which active and passive emissions become approximately equal defines a passive threshold level. At 14 dab, the cochlear amplifier gain was already at adult levels for the midfrequencies (4-8 kHz), but no emissions were detected at the extremes (at 1 kHz, and 24 kHz and above). During the period over which the endocochlear potential (EP) is known to increase most sharply (14 to 18 dab), the gain at all frequencies increased. At low frequencies there was little or no gain in the youngest age group, but matured by 23 dab. The gain at the middle frequencies subsequently decreased, resulting by 30 dab in a gain that was remarkably flat across frequency from 1 to 32 kHz. The passive thresholds generally improved with age at all frequencies, but most dramatically at the high frequencies. Results are consistent with the view that the elements of the cochlear amplifier are functional in the base of the cochlea at all ages, but that auditory function is primarily limited by the lower passive base cutoff frequency at younger ages. The proposed increase in passive base cutoff frequency with age accounts for the known place code shift.

Animals↗

PubMed1995

A 40 kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K-12 chromosome.

Many Salmonella typhimurium genes are required for bacterial entry into host cells. P22 transduction analysis has localized several invasion loci near minute 59 on the S. typhimurium chromosome. To further characterize the 59-60 min chromosomal region, we determined the physical and genetic map of 85 kb of S. typhimurium DNA between srl and cysC. It was previously shown that some of the invasion genes from this region are not present in Escherichia coli K-12. We examined whether other S. typhimurium genes on the 85 kb of DNA were similarly absent from E. coli. We found that a contiguous 40 kb fragment of the S. typhimurium chromosome which encodes invasion genes is absent from the corresponding region of the E. coli K-12 chromosome and may represent a 'pathogenicity island'. We speculate that acquisition of the 40 kb region must have significantly advanced the evolution of Salmonella as a pathogen.

Base Sequence↗

PubMed1995

Effects of furosemide on distortion product otoacoustic emissions and on neuronal responses in the anteroventral cochlear nucleus.

1. The objective of this study was to precisely evaluate the relationship between the threshold of neurons in the anteroventral cochlear nucleus (AVCN) and the properties of distortion product otoacoustic emissions (DPOAEs). Response areas of multiunit clusters in the AVCN and DPOAEs in the ear canal were measured alternately in the adult gerbil during furosemide-induced changes of the endocochlear potential. Stimulus frequencies of the probe tones for DPOAE measurement were in the range of f1 = 1.7-7.6 kHz and f2 = 2.0-9.0 kHz; the ratio f2:f1 was always 1.18. Stimulus amplitudes were varied in 5-dB steps from 30 to 80 dB SPL, with either equal amplitudes (L1 = L2) or unequal, with L1 set 10 dB above L2. Multiunit response areas were determined from cluster responses to a series of 100-ms tone bursts presented with a pseudo-random sequence in frequency and intensity. 2. Changes in the multiunit discharge properties after 50-75 mg/kg furosemide injection were as follows: the best frequency (BF) threshold increased from initial values in the range of 20-30 dB SPL to 50-80 dB SPL at 10-20 min postinjection and then recovered fully by 60-90 min. The spontaneous discharge activity decreased to zero before any changes in the frequency threshold curve were observed and did not return to initial values for several hours. Likewise, total discharge rates of stimulus elicited responses were reduced and tended to stay reduced even after BF threshold had fully recovered. 3. From the DPOAE measurements, the changes observed in the cubic distortion tone (CDT, 2f1-f2) emission after furosemide injection were as follows: at high levels of the probe tones, changes in the emission intensities generally stayed within a 10-dB range. The CDT amplitudes for low stimulus levels, however, were typically reduced by up to 40 dB, but recovered (depending on the furosemide dosage) by approximately 60-90 min. 4. At low to moderate stimulus levels of 40-60 dB SPL, there was a near perfect, minute-by-minute covariation of the ear canal CDT amplitude and the BF threshold measured in the AVCN. A 10-dB increase in threshold was associated with a 5- to 7-dB decrease in the CDT emission. 5. The optimum stimulus parameter set for the noninvasive estimation of cochlear performance from the CDT response was for stimulus amplitudes L1 = 50, L2 = 40 dB SPL. 6. This experiment demonstrates that CDT emissions at low stimulus levels are very good predictors of the thresholds of cochlear afferents, but this validity is lost for BF thresholds greater than approximately 60-70 dB SPL. 7. The ear canal CDT amplitude is better correlated with the BF threshold sensitivity of neuronal response areas in the AVCN than with the spontaneous discharge rate or absolute above-threshold discharge rates.

Animals↗

PubMed1994

Variation of distortion product otoacoustic emissions with furosemide injection.

Cochlear function was monitored in adult gerbils using distortion product otoacoustic emissions (DPOAE) during intraperitoneal injection of furosemide. All stimulus parameters were varied independently over a wide range, the stimulus frequencies f1 and f2 from 1 to 16 kHz, and the stimulus levels L1 and L2 from 20 to 80 dB SPL. The observed emissions at 2f1-f2 and 3f1-2f2 could be considered to be made up of two distinct components: (1) an 'active' source which depended in a complex way on the stimulus frequencies and levels, which was dominant at low and moderate stimulus levels, and which, by definition, was eliminated by sufficient furosemide intoxication; and (2) a 'passive' source which was essentially the same at all frequencies, with a level dependence given approximately by a simple power law distribution. The change from the active to the passive source was usually accompanied by an abrupt shift in emission phase angle. A simple summation model was shown to account for the observed form of this transition. The amount of the decrease in 2f1-f2 emission amplitude after furosemide injection was approximately independent of frequency and consistent for the middle frequency ratios and intensity levels (f2/f1 approximately equal to 1.3, L1 x L2 approximately equal to 55 x 50 dB SPL). It was concluded that the combination of DPOAE with furosemide injection can usefully be employed as a probe of active cochlear mechanics.

Acoustic Stimulation↗

PubMed1993

Vulnerability and adaptation of distortion product otoacoustic emissions to endocochlear potential variation.

The endocochlear potential (EP) was reversibly decreased in adult gerbils by the intraperitoneal injection of furosemide, while cochlear functioning was monitored by measurement of distortion production otoacoustic emissions (DPE) at a range of stimulus intensities. Stimulus frequencies for DPEs were f1 = 6.8 and f2 = 8 kHz (f2/f1 = 1.18). Emissions monitored in the ear canal and scala media were 2f1-f2, 3f1-2f2, 2f2-f1, and f2-f1. Typically, the EP decreased smoothly, reached a minimum one-half hour after injection, then recovered slowly over several hours. Emissions at 2f1-f2 and 3f1-2f2 at low stimulus levels were particularly vulnerable to the change in EP. These vulnerable emissions showed characteristic trajectories in which the amplitudes changed little with the initial EP decrease, then dropped sharply as the EP continued to decrease. However, the amplitudes then began to recover even before the EP reached minimum, and recovered completely while the EP remained subnormal. The trajectories of the other odd order emissions were similar, but lacked the abrupt decrease. The variation of the even order (f2-f1) component was completely different, but appeared related to the odd order trajectories in a complex fashion. During the initial decrease for the vulnerable components, the decrease in emission amplitude (in dB) was found to be proportional to the square of the change in EP (in mV). The recovery with a subnormal EP was interpreted as an adaptive effect with a time constant of about 15 min.

Acoustic Stimulation↗

PubMed1992

Binaural cochlear implants.

With the success of monaural cochlear implantation, patients frequently ask about having a second implant. We have performed binaural cochlear implants in 12 adult patients. Desire not to disrupt a functioning implant was the primary consideration in implanting the contralateral ear. Seven patients received a second 3M/House single-channel implant to upgrade to a magnetic external receiver. Four patients with a 3M/House device in one ear elected to place a Nucleus multichannel implant in the opposite ear. One patient with a poorly functioning Nucleus device elected to have a second Nucleus device. Four patients with a Nucleus and a 3M/House implant, one with binaural 3M/House implants, and one with binaural Nucleus implants were tested for auditory discrimination in order to quantify monaural versus binaural differences. The functional benefit of the second implant was mixed, but all patients showed some degree of objective improvement on one or more tests. Five of the six are regular users of both devices; the patient with binaural Nucleus implants wears only one. Despite the differing processing schemes, patients with a Nucleus device in one ear and a 3M/House device in the other ear are able to combine the two signals to advantage. We feel that cochlear implantation in the contralateral ear is an acceptable option in selected patients desiring an upgraded implant without placing a functioning implant at risk.

Aged↗

PubMed1991

Long-term follow-up evaluation of 1000 consecutive cemented total knee arthroplasties.

This is a report of a retrospective study of 1000 consecutive, cemented total knee arthroplasties performed by one surgeon from January 1976 to August 1989. Eighty-five percent of the patients were available after a mean of 51 months. Using The Knee Society Clinical Rating System, a good to excellent result was found in 95% of the knees; function was good to excellent in 54% of the knees. By using an actuarial method, 94% of the knees can be expected to survive 13 years. A deep venous thrombosis or pulmonary embolus was found in 1.7% and was no less common in the 25% of the patients who received pharmacologic anticoagulation. The mortality rate was 0.4%. The infection rate was 0.7% and did not correlate with intraoperative cultures. There were 14 failures for a variety of reasons, and six unsuccessful knees were revised. Preoperative medical problems did not generally predict the postoperative complications. The average duration of hospitalization during the last five years of the study was 9.7 days. Careful and consistent preoperative, intraoperative, and postoperative care is responsible for the low complication rate. The cemented knee arthroplasty consistently continues to yield good results.

Adult↗

PubMed1990

Proteinaceous lymphadenopathy due to monoclonal nonamyloid immunoglobulin deposit disease.

We report two cases of lymph node enlargement due to massive extracellular nonamyloid immunoglobulin deposits that obscured the underlying cellular pathologic condition. In both cases, the deposits were demonstrated to be restricted to a single heavy and light chain, consistent with a monoclonal paraprotein, and cytoplasmic staining in the lymphocytes or plasma cells was identical to that of the paraprotein. The use of the protein A-gold technique was instrumental in revealing a monoclonal pattern in one case in which light microscopic immunohistochemistry did not reveal a clear-cut monoclonal pattern in the extracellular deposits. This case was subsequently shown to have multiple myeloma, while the second case has had an unusual history of hypocomplementemic vasculitis and normal bone marrow. Neither case had evidence of significant renal disease.

Adult↗

PubMed1986

Extended X-ray absorption fine structure of Mn2+ and Mn2+ X ATP complex bound to coupling factor 1 of the H+-ATPase from chloroplasts.

The spinach chloroplast ATPase, coupling factor 1, contains three tight Mn2+-binding sites which interact cooperatively. The bound manganese coordinations were studied by x-ray absorption fine structure analysis. Mn2+ was found to be bound to the enzyme with an average Mn-O bond length of 2.15 +/- 0.15 A, significantly shorter than the 2.15 +/- 0.15 A of the Mn-O bond of the average first hydration shell for Mn2+ in aqueous solution. On adding ATP to the manganese-enzyme mixture, a tertiary complex of Mn2+ X ATP X enzyme was formed as indicated by the appearance of a second shell. Mn-P bond distances were estimated at 4.95 +/- 0.15 A in the tertiary Mn2+ X ATP X enzyme complex, which was considerably longer than the Mn-P bond distance of 3.36 +/- 0.15 A for the Mn2+ X ATP complex in aqueous solution. The Mn-P bond distance in the tertiary Mn2+ X ATP X enzyme complex decreased to 4.32 +/- 0.15 A when selenite, a potent effector of ATPase activity, was added. Based on these results, it is suggested that the tertiary complex is required for catalysis. The stimulation of ATP hydrolysis by anions such as selenite may be the result of shortening the distance between Mn2+ and the ATP phosphates in the enzyme active site.

Adenosine Triphosphate↗

PubMed1986

Latency and amplitude effects of electrode placement on the early auditory evoked response.

This study examined the effects of electrode placement on the early auditory evoked response in normally hearing subjects. The electrodes are termed noninverting, inverting, and common. Ten commonly used electrode combinations were evaluated. Both amplitudes and latencies of Waves I, III, and V were measured for each electrode combination. No mean differences in latencies were observed for Waves I, III, or V with any of the 10 electrode combinations. Similarly, no statistically significant Wave I or Wave III amplitude differences were found among the 10 electrode montages. However, larger Wave V amplitudes were found with placement of the noninverting electrode at the vertex (0.53 mu v) as compared to the upper forehead (0.39 mu v). Moreover, Wave V amplitudes were larger for inverting/common electrode placements at the seventh cervical vertebra/forehead, neck/forehead, and neck/neck (approximately 0.50 mu v) than for mastoid/mastoid and mastoid/forehead placements (approximately 0.40 mu v). Thus, three combinations of electrodes gave the largest Wave V amplitudes. These placements for the noninverting, inverting, and common electrodes, respectively, were (a) vertex-seventh-forehead, (b) vertex-neck-forehead, and (c) vertex-neck-neck.

Adolescent↗

PubMed1986

Oncocytoma of the lacrimal caruncle.

Two cases of oncocytoma of the lacrimal caruncle are presented. This benign tumour is characterized by a uniform population of epithelial cells with abundant, finely granular, eosinophilic cytoplasm. The granules stain blue with Mallorys phosphotungstic acid hematoxylin and can be identified as mitochondria by electron microscopy. An additional 35 cases from the literature are reviewed. The tumour usually occurs in people over the age of 60 years and is more common in women (male:female ratio of 1:5).

Adenoma↗