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A 3-year-old Collie bitch was euthanatized two weeks after the onset of blindness and deafness. The hearing deficit had been localized by clinical signs, brain stem auditory evoked responses, and impedance audiometry. Protothecosis was diagnosed by cytologic and histologic examinations. The organism was identified as Prototheca zopfii . Organisms and granulomatous lesions were found in kidney, heart, liver, skeletal muscle, thyroid gland, colon, bronchial lymph node, brain, and cochlea.

Simultaneous [14C]inulin and exogenous creatinine clearance procedures were performed on 10 healthy adult dogs of both sexes after constant IV infusions of inulin and a single subcutaneous injection of creatinine. For 30 clearance procedures determined for 10 dogs, the creatinine/inulin (C/I) clearance ratio was 1.03 +/- 0.01, and the results of the 2 tests were highly correlated (r = 0.91). Simultaneous [14C]inulin and endogenous creatinine clearance procedures were performed in the same 10 dogs. For 30 clearance procedures in these dogs, the C/I clearance ratio was 0.70 +/- 0.06 and the 2 tests were less highly correlated (r = 0.79). Fifteen clearance procedures of the same design were conducted on 5 dogs with azotemia induced by surgical reduction of renal mass. In these dogs, the exogenous C/I clearance ratio was 1.09 +/- 0.12, and the endogenous C/I clearance ratio was 0.89 +/- 0.07. It was concluded that the single injection method of exogenous creatinine clearance was a valid method for clinical measurement of glomerular filtration rate in the female dog and would closely approximate glomerular filtration rate in male dogs without azotemia. At normal or near normal plasma creatinine levels, the endogenous creatinine clearance procedure gave erroneously low values for glomerular filtration rate when the common methods of creatinine analysis were used.

A barbiturate (phenobarbital or primidone) was withdrawn over a period of 3 months from 25 institutionalized residents, all of whom had had three seizures or less in the past 6 months and were maintained on a nonsedating drug (phenytoin, carbamazepine, or valproic acid). Results were compared with a matched comparison group maintained on both drugs. Subjects withdrawn from primidone, but not those withdrawn from phenobarbital, had increased seizure frequency, probably due to withdrawal. After 14 months, seizure-free subjects withdrawn from barbiturates were no more likely to have had seizures than were comparison subjects. Barbiturates appear to be unnecessary and may be withdrawn.

Heart rate and arterial systolic, mean, and diastolic blood pressures were measured indirectly in apparently healthy dogs in clinical situations (examination rooms, cages, or runs) and in 3 groups of abnormal dogs. An electronic automatic sphygmomanometer measured and analyzed arterial pulses (oscillometric method). Apparently healthy dogs had a mean +/- SD heart rate of 134 +/- 32 beats/min and systolic, mean, and diastolic pressures of 144 +/- 27, 110 +/- 21, and 91 +/- 20 mm of Hg, respectively. The mean systolic pressure was significantly higher in hospitalized dogs than in nonhospitalized dogs. When compared with relaxed dogs, playful dogs had a higher mean heart rate. Apprehensive dogs had a higher mean diastolic pressure than did relaxed dogs. The mean heart rate and blood pressures of panting dogs were not significantly different from the mean values from relaxed dogs. Heavier (greater than 18 kg) and older (greater than 2 years) dogs had lower mean heart rates and higher pressures, compared with lighter (less than or equal to 18 kg) and younger (less than or equal to 2 years) dogs. Infection with Dirofilaria immitis had no effect on heart rate and blood pressures when compared with apparently healthy dogs. Dogs with renal failure had a significantly higher mean diastolic pressure and dogs with mitral regurgitation had a significantly lower mean diastolic pressure, compared with apparently healthy dogs.

The Intensive Medicines Monitoring Programme (IMP), a specialised part of the New Zealand Post Marketing Surveillance system, has been used to monitor captopril since it was first approved for marketing for the treatment of hypertension and heart failure. Monitoring has consisted of (1) spontaneous reporting for which doctors have been encouraged to report all clinical events, (2) a specific event recording survey at the end of the first year and (3) a controlled patient survey of taste disturbance. The IMP gathers prescription information on about 85% of all patients. There were 4,124 patients at the end of the first 4 years. Reported events involved 4% of patients, the majority being cutaneous (1%) and gastrointestinal (0.7%). The event recording survey gave an overall rate of adverse events of 2.2 per patient year. The taste survey showed a remarkably high incidence of taste disturbance in the control population and only taste loss was significantly higher (P less than 0.01) for captopril. This ongoing study has so far demonstrated a low incidence of adverse effects due to captopril, which is reassuring in view of its increasing use for mild hypertension and early cardiac failure.

The cytotoxicity of vincristine (VCR), beta-cytosine arabinoside (Ara-C), or adriamycin (ADRIA) in combination with 5-azacytidine (Aza-CR) to L1210 leukemia in vivo was measured to determine if schedule-dependent synergistic or antagonistic drug interaction occurred. Two dose levels of Aza-CR were studied (0.1 and 0.5 mg/mouse), and cytotoxicity was measured by the spleen colony assay. For the combination of Aza-CR plus VCR, cytotoxicity was essentially additive or antagonistic when VCR preceded Aza-CR and additive or synergistic when VCR followed Aza-CR. When Aza-CR was combined simultaneously with either Ara-C or ADRIA, cytotoxicity was markedly antagonistic but was additive if drugs were given sequentially. When Ara-C was given as a 24-hour infusion before Aza-CR, the resultant cell kill was antagonistic (although slightly greater than that obtained for Ara-C alone). However, antagonism was even more marked when Aza-CR was given before the 24-hour infusion of Ara-C; cell kill was less than that observed with Ara-CR alone. Synergistic cytotoxicity was observed only with VCR administered after a low dose of of Aza-CR. Therefore, scheduling of drugs in combination with Aza-CR may be critical in the determination of the antileukemic cytotoxic effects.

Electroretinograms (ERG) and visual evoked responses (VER) were recorded from 2 anesthetized dogs before and after surgical manipulation. The ERG was recorded from a corneal contact lens, and the VET, from 9 different scalp sites. The recordings were made on a signal averager as done in clinical situations. Surgical manipulation consisted of an alcohol block of the stimulated eye and enucleation of the nonstimulated eye. The results indicated that under the conditions of making the recordings, the major and consistent waves of the VER from all scalp sites were a far-field ERG and were not of cortical origin.

The orientations (angles) of mean QRS vectors were manually calculated from scaler orthogonal leads (I, aVf, V10; X, Y, Z) and from X-Y oscilloscope recordings from cats injected with ketamine and acetylpromazine. Those angles calculated from individually recorded leads (I, aVf, and V10) were from cats in right lateral and sternal recumbency. Leads, X, Y, and Z were recorded simultaneously from cats in the sternal recumbency. The oscilloscope recordings were derived from the X, Y, and Z leads. Arithmetic and maximal measurements from ECG scaler leads and maximal and half-area measurements from oscilloscopic recordings were used for calculations. Recordings from 15 cats and from 1 cat 15 times. Based on visual inspection of scattergrams, the X, Y, and Z vectors were not different in orientation from I, aVf, and V10 vectors. Orientation of oscilloscopic vectors were more variable than orientations of vectors calculated from scaler leads. Body position of the cat during recording did not affect mean values of angles derived from leads I, aVf, and V10. Type of measurements did not affect mean values. Variation of orientation was greater among cats than for the intraindividual vector orientations. Configuration and direction of QRS loops from 27 normal cats were also recorded. The greatest variation in loop configuration was in the frontal plane.

Neomycin sulfate was administered intravenously to eight mixed-breed dogs at a dosage of 30 mg/kg/day for as long as 50 days. Auditory-evoked brain stem potentials (AEBP) were recorded from the dogs three times a week. The AEBP amplitudes and latencies from the eight treated and the eight control dogs were compared. All treated dogs eventually exhibited an isoelectric AEBP. The time required for the AEBP waveform loss to occur in the treated dogs varied between 22 and 50 days. The AEBP waveforms were still isoelectric when measured as long as 150 days after neomycin administration was stopped. The fact that AEBP did not return would tend to support the findings of others that the loss of the receptors in the inner ear, due to neomycin toxicity, is permanent. The results of this electrophysiologic study indicate that the organ of Corti (organum spirale) is the site of pathologic changes in the auditory system that result from neomycin treatment.

Kinetics of gentamicin (2.2 mg/kg of body weight) were investigated in 7 sheep after IV bolus administration. The mean serum concentration profile could be described by a 2-compartment open model with a distribution rate constant (alpha) of 3.112 +/- 1.681 hour-1 [half-life, t1/2(alpha) = 17.22 +/- 8.63 minutes] and an overall elimination rate constant (beta) of 0.485 +/- 0.028 hour-1 [t1/2(beta) - 85.87 +/- 5.03 minutes]. The apparent volume of distribution was somewhat restricted [Vd(area) = 0.194 +/- 0.059 L/Kg], and the total body clearance was 1.559 +/- 0.400 ml/kg/min. Equal dosages of gentamicin (2.2 mg/kg) were also given IM and intratracheally (IT). after IM injection, gentamicin reached peak serum concentration at postinjection minutes (PIM) 45, surpassing concentrations after the IV injection for the remainder of the experiment. The IT injection produced detectable serum concentrations at PIM 5, with a peak concentration at PIM 60. The serum drug concentrations after IT injections remained well below concentrations after IV and IM injections. Radiographic analysis of an IT injection of a gentamicin-tantalum suspension revealed good distribution throughout the trachea and proximal bronchi, with physical clearance of the tantalum occurring after greater than or equal to 10 minutes. Aspiration biopsy of the tracheal wash 6 hours after IT gentamicin injection revealed no cytologic response to gentamicin in 6 of 7 sheep, with the single response that of a purulent exudate.

A preliminary experiment to measure the existence of signal coherency over very long baselines is described. Data for these measurements was obtained by NRL with the cooperation of USNUSL in allowing collaboration with their previously scheduled ARTEMIS propagation experiment. The data was recorded at SOSUS stations, mostly by NRL personnel for data processing at the Laboratory via digital computer. Initial results indicate the correlation coefficient of about 0.35 observed for one data run over a baseline distance of 450 nm. Additional field collection and laboratory analysis are planned to establish the range of possible values with greater accuracy and consistency. These studies are believed relevant to Navy needs, as follows: (1) research evaluation of methods of on-line processing of signals brought to a central point from several SOSUS arrays; (2) study of long range acoustic propagation to widely separated reception points; and (3) consideration of methods of target localization by triangulation from two or more widely spaced arrays. In addition to the above, there is some indication of possible jamming effects on SOSUS stations in the upper portion of the frequency range, by pseudo-random noise signals of sequence length utilized for this experiment. Follow-on experiments to further illuminate the above problem areas are planned.

Sidetone delay (delayed auditory feedback) is known to cause speakers to talk more slowly, and at delays of about 200 ms also causes severe articulation disturbances. If shorter delays can slow speech without adverse effects on articulation, this effect could be used to make talkers speak more slowly in certain communications situations. Subjects read lists of 1, 2, 3, or 4 syllable words and of sentences under each of 6 delay conditions (0, 7.5, 15, 30, 60, and 100 ms). Delays of 15–30 ms caused a significant slowdown in speaking rate with no adverse effects on articulation. Delays of 60–100 ms caused a greater slowdown but also had a noticeable adverse effect on speech quality, especially for sentences and polysyllablic lists. In communications situations where the quality of transmitted speech is degraded (e.g., vocoded speech), sidetone delay may be useful in modifying the talk's behavior to improve overall speech quality.

Method and results are presented for the application of statistical pattern‐recognition techniques to automatic classification of words and talkers using formant‐tracking data as the input. The method employs the expression of an entire formant pattern as a single n‐dimensional vector. Each vector component represents a sample of one of the formant functions at a giventime. Thus, the dimensionality of the n space is determined by the product of the number of formant parameters sampled and the number of observation epochs. A computer program processes these data in two steps. In the first step, called a “learning” program, separate statistical categories are established by the computation of the mean vector and covariance matrix describing a normal distribution function for the set of vectors that define each category. In the second step, called the “recognition” program, an unknown is recognized by computing the statistical distance to all possible categories and selecting the category for which this distance is minimum. Results, in the form of confusion matrices, are presented for word recognition of the first ten letters of the alphabet as spoken by 10 talkers and for recognition of the talkers.

In a formant‐tracking vocoder, any lag in acquiring correct formant‐frequency values, after the release of a consonant, produces false formant transitions; these may cause an error in transmission of the consonant. Tracking of the second formant (F2) is especially critical in this respect. In the present study, some means of predicting F2 are presented. F2 relations across consonant constrictions were measured in spectrograms of the spontaneous speech of five male speakers. The study compared prediction of the frequency of postconsonantal F2 by three extrapolations of preconsonantal F2: (1) holding the last value; (2) linear extrapolation of the last course; and (3) exponential extrapolation of the last course. Holding and exponential extrapolation were superior to linear extrapolation. Mean prediction error was about 300 cps with the two better methods. Errors were then partitioned according to upward or downward last course, in conjunction with high‐middle, or low‐frequency regions for the beginning of extrapolation. Certain partitionings reduced mean prediction error to 200 cps. [Research supported in part by the U. S. Army Electronics Research and Development Laboratory.]

Work with a voice‐excited formant vocoder has led to experiments on several other methods of processing speech. These methods make use of the baseband and some of the same types of information which are normally derived by a formant vocoder, such as front‐back vowel detection and voice‐voiceless discrimination, but applied in a manner different from a normal formant vocoder. The systems so far tested are characterized by transmission of the baseband in unprocessed form and the regeneration of higher frequency information by deriving it from the baseband or simple parameters. While these systems do not yield high quality speech, the intelligibility may be high enough for certain limited applications. Tape recordings of these systems will be presented.

A formant‐tracking method based on the measure of majority period is discussed. This tracker employs as input data the instantaneous period measures of formants that have been selected by appropriate formant‐range filters. These periods are subjected to an electronic circuit that, by a unique feedback arrangement, suppresses periods that deviate beyond a fixed threshold distance from the mean period. The resulting circuit output very nearly tracks the majority period of the set of periods that originally comprised the input data. The method also incorporates a means of weighting the majority period formant measure toward the median of the formant range. By this means, the tendency to be captured by adjacent formants is significantly reduced. The paper describes the method of implementation and the application of the method to formant tracking in the second‐formant range. [Research supported in part by U. S. Army Electronics Research and Development Laboratory.]

The formant vocoder has now been under investigation for use as a speech‐compression system for more than a decade. During that time, significant advances have been made in the technology of the analysis and synthesis portions of the formant vocoder, and in the encoding of the parametric control signals for communication of the speech information at data rates normally of 1200 bit/sec and as low as 600 bit/sec. The consequence has been considerably improved vocal quality and articulation. Also, a voice‐excited operation mode has been developed for the formant vocoder that is designed to provide high‐quality speech transmission at a data rate of 4800 bit/sec. In this paper, some of the more important aspects of the formant‐vocoder system design are to be discussed. These include adaptive techniques for formant‐frequency tracking the use of the serial vocal analog for synthesis, encoding techniques for transmission of the vocoder parameters in binary form, and the voice‐excited mode of operation of the form...

This paper discusses design and performance of a speech‐compression system that incorporates a formant‐tracking vocoder for the analysis‐synthesis of the vocalic utterances in speech, and a channel vocoder with 5 fixed‐frequency channels and 1 tracking channel for the analysis‐synthesis of the nonvocalic utterances of speech. The information is multiplexed and transmitted over eight 25‐cps low‐pass analog channels. For vocalic utterances, the parameters transmitted are the first 3 formants, their respective amplitudes, the frequency of pitch, and a separate vocalic nonvocalic decision signal. For nonvocalic utterances, the information transmitted is the amplitude of 5 vocoder channels. and the frequency and amplitude of 1 tracking channel covering the range from 2300 to 6000 cps, used to control a variable‐frequency pole‐zero filter in the synthesizer. For male talkers, this system demonstrates a mean articulation score of 87%. Confusion matrices and a demonstration tape recording are presented.

One of the formant vocoder's principal promises lies in the more efficient encoding of the word information content of speech than can be achieved by the use of the more familiar channel vocoder. The consequence of this more efficient encoding manifests itself in the capability for encoding speech for binary‐encoded formant data at binary‐data rates potentially as low as 150 bits/sec. In this paper, various avenues of approach for achieving such low‐binary‐data‐rate transmission are explored for system operation at various data rates ranging from 150 to 1200 bits/sec. Results of recent laboratory tests are presented.