Central auditory processing of durational changes in complex speech patterns by newborns: an event-related brain potential study.

In this study, newborns' ability to discriminate durational changes in the fricative /s/ within a nonsense word was investigated. The results showed that infrequent increments and decrements of a speech sound duration elicit a mismatch negativity kind of response in sleeping human newborns. In the auditory event-related potential to these deviant stimuli two negative waves of this response were revealed. The first negative wave peaked at about 150 msec and the second at about 350 msec after the change onset. At least one negative deflection, which was interpreted as evidence for stimulus change-detection, was observed in every infant.

A study of the effects of lisinopril when used in addition to atenolol.

A double-blind, parallel group multicentre study was carried out to compare the effects of adding once daily treatment with lisinopril 10 or 20 mg and placebo to the treatment of 100 patients whose blood pressure was inadequately controlled with once daily atenolol 50 mg. Following a two-week run-in period, patients with a lying DBP between 95 mmHg and 115 mmHg were randomised to either lisinopril 10 mg or placebo once daily for four weeks. Blood pressure measurements were made approximately 24 h after the previous dose of study medication. After four weeks' treatment the dose of study medication was doubled for those patients whose lying DBP was greater than or equal to 90 mmHg and a final assessment was made after a further two weeks of treatment. Overall, six weeks' treatment with lisinopril produced a greater fall in lying blood pressures than placebo when added to atenolol therapy. The difference in favour of the additional ACE inhibitor therapy was 7.1 +/- 2.6/5.4 +/- 1.5 mmHg (mean +/- SEM) (P less than 0.01). Standing blood pressures showed similar behaviour in favour of the additional ACE inhibitor treatment (7.6 +/- 2.4/4.7 +/- 1.6 mmHg) (P less than 0.005). Heart rate was not altered significantly by either lisinopril or placebo treatment. The addition of lisinopril to treatment with atenolol produced a slight increase in the reported number of adverse events compared with placebo. The results of this study indicate that the addition of lisinopril 10-20 mg once daily to treatment with a beta-adrenoceptor blocking drug produces a worthwhile decrease in blood pressure in patients not responsive to beta-blocker therapy alone.

Effect of the Choice of Primary Chemotherapy on the Cumulative Length of Stay in Hospital for Multiple Myeloma.

The actual use of hospital beds for patients with multiple myeloma was calculated from a randomised trial of primary treatment with either melphalan and prednisone (MP, 66 patients) or intensive combination chemotherapy with vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA, 64 patients). The survival of the patients was similar in both arms, and the samples, 20 and 32 patients, respectively, were well representative for the whole arms. The average numbers of hospital days were similar fur both arms. For the first year MP 33.2 (SD 27.6) vs. MOCCA 32.1 (SD 19.0), and during the first to 4th years 78.5 (SD 45.9) vs. 67.8 (SD 34.1). For the year of death it was 50.4 (SD 33.1) vii. 36.3 (SD 27.0), respectivelly. Thus the choice of primary chemotherapy whether conventional or more aggressive had no influence on the actual number of in-patient hospital days concerned. When the combination chemotherapy schedule is well tolerated it can be administered just as well on an ambulatory basis or by using it with very short admissions. It seems that the need for inpatient care for patients with multiple myeloma is mostly related to the complications of the disease itself and to intercurrent disorders including infections.

The steady-state pharmacokinetics of tamoxifen and its metabolites in breast cancer patients.

The steady-state pharmacokinetics of tamoxifen and its metabolites was studied in sixteen patients with advanced mammary cancer. Patients were randomized to receive tamoxifen given as Tamofen, Leiras, or as Nolvadex, ICI, 20 mg twice daily for 16 weeks in a cross-over study. Plasma and urine samples were analyzed during one dose interval (12 h) after treatment for 8 and 16 weeks. The concentrations of tamoxifen, N-desmethyltamoxifen, N,N-desdimethyltamoxifen, and metabolite Y were determined in plasma and the areas under the plasma level curves were calculated. 4-Hydroxytamoxifen was not found in plasma. In urine samples only tamoxifen and N-desmethyltamoxifen were above the detection limits even though metabolite Y was also analyzed after acid hydrolysis. There were no statistically significant differences in the concentrations of tamoxifen and its metabolites between the two preparations. The results of nonresponders did not differ from those of responders. Liver metastases had no effect on the metabolism of tamoxifen.

Antianginal effect of isosorbide dinitrate spray in patients with exercise-induced stable angina.

Ten patients with stable exercise-induced angina took part in this study. Isosorbide dinitrate and placebo sprays were administered in a double-blind, randomized crossover study. The dose of isosorbide dinitrate given was two squirts (= 2.5 mg) 2 min before testing. When taken before exercise it significantly improved (p less than 0.014) exercise tolerance. Significant (p less than 0.0005) ischaemic changes in the electrocardiogram also occurred. These effects occurred later than with placebo. Exercise time was prolonged with the active drug. The results of this study show that isosorbide dinitrate spray improves the exercise tolerance of patients with ischaemic heart disease.

Vibrotactile atonal interval correlated with activity in peripheral mechanoreceptive units innervating the human hand.

The quality of sensations and the vibrotactile atonal interval-the gap between detection and vibration thresholds-were studied with vibratory stimuli of varying frequency (20, 80 and 160 Hz) and duration (100, 400 and 800 ms) applied to the hairy and glabrous skin of the hand. Detection and vibration thresholds were also determined while simultaneously recording single unit activity from the radial nerve innervating the hairy skin of the hand. Both thresholds were lower on the glabrous than the hairy skin, and the thresholds decreased on both skin areas with increasing vibration frequency. A sensation of short duration was elicited at detection threshold only with a 20-Hz stimulus of 100-ms duration; with other frequency-duration combinations sensations of longer duration were reported. Considerably larger vibration amplitudes were needed on both skin areas for the sensations to be unequivocal with respect to duration and pitch (vibration threshold). There was no significant effect of stimulus duration on vibrotactile thresholds. The width of the average atonal intervals was above 10 dB on both skin areas, and with increasing vibration frequency, decreasing values of atonal intervals were obtained on the hairy skin, whereas considerably increasing values were obtained on the glabrous skin. Recording of single unit activity indicates that on the hairy skin detection of the stimulus at 20 Hz is correlated with activation of slowly adapting (SA) type II and the most sensitive rapidly adapting (RA) units, while distinct vibratory sensations involve entrainment of RA units. Also at 80 Hz, non-pacinian units could contribute to the mechanism of vibrotactile thresholds, whereas at 160 Hz only pacinian (PC) units are involved.

Somatosensory evoked potentials associated with tactile stimulation at detection threshold in man.

Somatosensory evoked potentials elicited by sub- and supraliminal tactile pulses were studied during continuous threshold measurement. Two threshold methods were used: a modified tracking method and a detection method. With both methods threshold estimates of the same order of magnitude were obtained. Stimuli just above the threshold elicited a distinct somatosensory evoked potential with components P50, P100, N190 and P400. No such SEP was associated with the subliminal stimuli. However, in some cases some potential oscillations were obtained, time-locked to the subliminal stimuli; these are suggested to be due to errors in responding. In control experiments detected stimuli elicited a distinct SEP, but no SEP was associated with undetected stimuli of identical amplitude. The results indicate that in the psychophysical threshold determination the neural processing reflected in the SEP is associated only with supraliminal tactile stimulation. The lack of evoked brain activity associated with subliminal tactile stimuli supports the hypothesis derived from human microneurographic studies, stating that the tactile detection threshold may be based on an extremely small peripheral input, perhaps only on a single impulse in a single peripheral fiber.

Bioavailability of a combination preparation of trimethoprim and folic acid.

The bioavailability of folic acid and trimethoprim was investigated from a combination preparation of folic acid (0.25 mg) and trimethoprim (100 mg) in ten healthy adult volunteers. Peroral administration of the preparation resulted in a mean peak plasma concentration of trimethoprim 1.09 mg/l (SEM 0.06). The AUC values for trimethoprim were 12.42 mg.h/l and 12.77 mg.h/l corresponding to combination preparation and plain trimethoprim, p greater than 0.1. After administration 0.25 mg folic acid in the combination preparation, there was a significant rise in serum folic acid concentrations. The AUC from 0-8 hours was 199.8 nmol.h/l (SEM 8.1) and 166.3 nmol.h/l (SEM 14.2) corresponding to combination preparation and plain trimethoprim, p less than 0.001. A loading dose of folic acid 10 mg was given intramuscularly 24 hours before drug intake. This new type of formulation of trimethoprim and folic acid has been developed in order to prevent in long-term use the adverse haematological effects induced by trimethoprim alone.

Bioavailability of paediatric mixtures containing phenoxymethylpenicillin calcium or potassium salt.

The bioavailability of the calcium and potassium salts of phenoxymethyl-penicillin (dose 38,000 I.U./kg) was investigated in eight healthy adult volunteers. Administration of the calcium salt as an aqueous oral mixture resulted in a mean peak plasma concentration of 8.52 mg/l (SD 1 X 96) and that of the potassium salt mixture in a concentration of 8.40 mg/ml (SD 2.61), p greater than 0.1. The median time-to-peak levels were 0.75 h and 1.0 h, respectively (p greater than 0.1). The mean AUC for the calcium salt mixture was 16.94 mg X h/l (SD 3.31) and for the potassium salt 15.84 mg X h/l (SD 4.76), p less than 0.09. These findings confirm that an aqueous mixture of calcium phenoxymethylpenicillin is equivalent to a mixture of potassium phenoxymethylpenicillin.

Peripheral neural basis of tactile sensations in man: II. Characteristics of human mechanoreceptors in the hairy skin and correlations of their activity with tactile sensations.

Properties of the human mechanoreceptors in the hairy skin of the back of the hand were studied by microelectrode measurements from the radial nerve. Correlations of unit activity with sensations elicited by tactile pulses (single cycle sinusoids of 20, 60 and 150 HZ) were examined with simultaneous measurements of unit activity and sensation thresholds and magnitude. A total of 264 mechanoreceptive units were identified. Of all units 66% were classified as slowly adapting (SA) and 34% as rapidly adapting (RA) units. Mechanical thresholds of the units as well as simultaneously measured sensation thresholds decreased with increasing frequency of the pulse. The thresholds of several SA units were identical with the subjective thresholds. The responses of the units to supraliminal pulses consisted maximally of 7 impulses. Most SAI and RA units were able to code to some extent the stimulus amplitude on the basis of number of impulses, but only RA units had stimulus-response functions indicating velocity coding. Comparisons of the estimates of sensation magnitude with the number of impulses in the response indicated that the estimate may be based mainly on activity in a population of RA units. The comparison of the present results with earlier reports on properties of receptors in the glabrous skin of the human hand indicates that there are some differences between the characteristics of receptors in the hairy and glabrous skin. However, human receptors in the hairy skin do not seem to differ from the corresponding receptors in the animals.

Dry polyacrylamide batch method for determining the binding of various compounds by plasma proteins.

A new modification of the gel diffusion method has been developed using dry polyacrylamide gel. The theoretical background is explained and the mathematical formulas are presented. The properties of the gel are studied, concerning the absorbing capacities and changes in ion equilibria. As a model compound the freely diffusible calcium is assayed and the result obtained (52.4 +/- 2.9%) agrees well with the results from previous methods by other authors. The accuracy of the method is discussed and the theoretical explanation to the sensitivity in determinations is calculated.