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Biomedical subjects

H Kaplan

Publications and source records attributed to H Kaplan.

At least 163 records · Page 9Linked to original sources

Evaluation of zopiclone physical dependence liability in normal volunteers.

The potential of zopiclone, a non-benzodiazepine sedative hypnotic, to induce physical dependence in normal human volunteers was investigated. 9 male subjects (age range 21-39 years) participated in a 56-day double-blind study with random assignment to initial treatment A or B: (A) zopiclone 7.5 mg p.o. nightly for 21 days followed by placebo for 7 days, and (B) placebo nightly for 21 days followed by placebo for 7 days. Heart rate, blood pressure, hand tremor and auditory-evoked EEG were repeatedly measured during the withdrawal periods. No differences in any of these variables between phases were found (beta = 0.90 for mean differences of 16% between phases). Subjects slept longer (mean 28 min, p less than 0.013) on zopiclone than on placebo. Symptoms of state anxiety were greater on days 2 and 4 after discontinuing zopiclone compared to all other withdrawal days (p less than 0.0021). The mean relative increase on days 2 and 4 was 30%. Sleep depth (self-rating scale) was no deeper on drug than on placebo, but during the withdrawal phases, sleep was less deep on days 2 and 4 of withdrawal from zopiclone compared to all other withdrawal days (p less than 0.0001). Subjects were unable to identify the pattern of drug administration on withdrawal, and none reported important symptoms. Discontinuation of zopiclone (7.5 mg for 21 days) is associated with detectable increase in state anxiety and lighter sleep on days 2 and 4 of withdrawal. Quantitatively, similar changes occur with other hypnotic drugs of relatively low dependence liability.

Adult↗

Aspirin and prostacyclin treatment of diabetic dogs.

Spontaneously diabetic dogs were treated initially (the first 1/2 yr) with i.v. prostacyclin and oral aspirin and then for 1 yr with varying doses of aspirin alone. At this time cataracts prevented visualization of retinae, and one eye of each animal was removed for examination of the vasculature of the trypsin digested retinae. Studies of the blood during the course of treatment showed an elevation of plasma cyclic adenylic acid and marked lowering of inordinately high platelet count and platelet aggregation. Treatment was stopped and after an additional 1/2 year the animals were euthanized and the fellow eye removed for retinal study. Although just three diabetic animals survived for binocular retinal histology, there were no discernible differences in the retinal vasculature in the fellow eyes of a given animal, and in only one of these three animals were there clear signs of diabetic retinopathy. We must conclude, therefore, that in spite of relative normalization of platelet function in the parameters measured during the course of treatment, we cannot yet claim a salutary effect of treatment on the diabetic retina. Cataracts prevented us from having better information on diabetic retinae prior to treatment and a redesigned study would have to include unilateral histological retinal examination before any treatment is started to determine if, indeed, improved platelet physiology slows or reverses changes in the diabetic retina.

Animals↗

Chemical properties of the N-termini of human haemoglobin.

The chemical properties, namely pK and reactivity, of the N-termini of oxyhaemoglobin and deoxyhaemoglobin toward acetic anhydride and 1-fluoro-2,4-dinitrobenzene (Dnp-F) were determined by the competitive-labelling approach [Kaplan, Stevenson & Hartley, (1971) Biochem. J. 124, 289-229; Duggleby & Kaplan (1975) Biochemistry 14, 5168-5175]. At physiological pH and temperature, the valine-1 alpha and valine-1-beta amino groups had unusually low pK values, but showed only minimal changes in their pK values on deoxygenation. Between pH 7.5 and pH 8.0 a deviation was observed in the pH-reactivity profiles and the apparent pK values became markedly pH-dependent. It was found that Dnp-F, but not acetic anhydride, had an abnormally high reactivity toward the N-termini. It is concluded that the valine-1 alpha and valine-1 beta N-termini make little or no contribution to the alkaline Bohr effect at physiological pH values. The high reactivity toward Dnp-F is attributed to an interaction or binding near the N-terminal region, and the discontinuity in the pH-reactivity profile at moderate alkaline pH values to a conformational change which alters the environment of these groups.

Acetic Anhydrides↗

Brain vasculature and induced ischemia in seizure-prone and non-seizure-prone gerbils.

The relationship between seizure propensity and the vascular anatomy of the anterior cerebral arteries, or stroke induced by unilateral ligation of the common carotid artery, was investigated utilizing well differentiated colonies of seizure-prone (SP) and non-seizure-prone (NSP) gerbils. Twenty SP and 20 NSP gerbils were perfused with a latex dye and the vascular patterns of the anterior cerebral arteries (ACA) were analyzed. In addition, 30 SP and 30 NSP gerbils were subjected to unilateral ligation of the common carotid artery and the number developing stroke (determined by clinical observation as well as by microscopic examination of the brain) was recorded. We found that in all animals the ACAs formed a fused-central vessel which vascularized the olfactory bulbs, as well as two lateral vessels (rostral arteries) that vascularized a previously undescribed nasal plexus. Neither the vascular pattern of the ACA, nor the frequency of occurrence of stroke following unilateral ligation was related to seizure propensity.

Animals↗

The constituents of fresh frozen plasma stored with citrate phosphate dextrose and their clinical implications.

The authors have investigated the constituents of fresh frozen plasma stored in citrate phosphate dextrose (CPD) at -20 degrees C. The results indicate abnormal characteristics of several of the constituents, whereas some others remain within normal values. This is attributed to preparation procedures with the addition of a CPD solution. Fresh frozen plasma being hyperosmolal, hypernatremic, hyperglycemic, hyperphosphatemic, normokalemic and containing normal values of protein, calcium, magnesium, and water carries a clinical implication for the physician as a guide for the treatment of the critically ill patient when large amounts of plasma are needed.

Blood Glucose↗

Differences in speech discrimination in the elderly as a function of type of competing noise: speech-babble or cafeteria.

Speech discrimination of place-loaded Modified Rhyme test words in speech-babble and cafeteria noise by elderly hearing-impaired subjects was measured. The stimuli were presented under the following conditions: (1) monotic: the signal was presented to the preferred ear; (2) low-frequency attenuated: the frequency band below 1,000 Hz was attenuated by 5, 10, and 15 dB relative to the high-frequency band; (3) dichotic: the frequency band above 1,000 Hz was presented to the preferred ear and the low-frequency band to the other ear; (4) diotic: the same signal was presented to both ears. Difference scores between the monotic baseline condition and the other listening modes were calculated and compared. Relationships between listening modes differed as a function of type of competing noise. Low-frequency attenuation improved discrimination in speech-babble but not in cafeteria noise. Dichotic-monotic and diotic-monotic superiority were seen with both noises.

Aged↗

[Changes in the elastic tissue of patients with Down's syndrome].

Two patients with Down's syndrome are reported. A concomitant finding in one of them was psoriasis (not frequent in these patients), anetoderma and unelastic connective tissue nevi. Anetoderma was the only concomitant finding in the other patients. On the basis of these findings the authors feel that besides the "stigmata" referred to, patients with Down's syndrome may present congenital malformation of the elastic fibers. Another objective of this paper is to suggest that every one of these patients should be submitted to a through dermatological investigation having regard to the highly varied and interesting skin changes likely to be disclosed.

Adult↗

Evaluation of zopiclone physical dependence liability in normal volunteers.

The potential of zopiclone, a non-benzodiazepine sedative hypnotic, to induce physical dependence in normal human volunteers was investigated. 9 male subjects (age range 21-39 years) participated in a 56-day double-blind study with random assignment to initial treatment A or B: (A) zopiclone 7.5 mg p.o. nightly for 21 days followed by placebo for 7 days, and (B) placebo nightly for 21 days followed by placebo for 7 days. Heart rate, blood pressure, hand tremor and auditory-evoked EEG were repeatedly measured during the withdrawal periods. No differences in any of these variables between phases were found (beta = 0.90 for mean differences of 16% between phases). Subjects slept longer (mean 28 min, p less than 0.013) on zopiclone than on placebo. Symptoms of state anxiety were greater on days 2 and 4 after discontinuing zopiclone compared to all other withdrawal days (p less than 0.0021). The mean relative increase on days 2 and 4 was 30%. Sleep depth (self-rating scale) was no deeper on drug than on placebo, but during the withdrawal phases, sleep was less deep on days 2 and 4 of withdrawal from zopiclone compared to all other withdrawal days (p less than 0.0001). Subjects were unable to identify the pattern of drug administration on withdrawal, and none reported important symptoms. Discontinuation of zopiclone (7.5 mg for 21 days) is associated with detectable increase in state anxiety and lighter sleep on days 2 and 4 of withdrawal. Quantitatively, similar changes occur with other hypnotic drugs of relatively low dependence liability.

Adult↗

Chemical properties of the functional groups of insulin.

The method of competitive binding [Kaplan, Stevenson & Hartley (1971) Biochem. J. 124, 289-299] with 1-fluoro-2,4-dinitrobenzene as the labelling reagent [Duggleby & Kaplan (1975) Biochemistry 14, 5168-5175] was used to determine the chemical properties, namely pK and reactivity, of the amino groups, the histidine residues and the tyrosine residues of the dimeric form of pig zinc-free insulin at 20.0 degrees C. The N-terminal glycine residue of the A-chain has a pK of 7.7 and a slightly higher than normal reactivity. The N-terminal phenylalanine residue of the B-chain has a pK of 6.9 and is approximately an order of magnitude more reactive than a corresponding amino group with the same pK value. The lysine epsilon-amino group has an unusually low pK of 7.0 but has approximately the expected reactivity of such a group. In the case of the two histidine and four tyrosine residues only the average properties of each class were determined. The histidine residues have a pK value of approx. 6.6, but, however, their reactivity is at least an order of magnitude greater than that of a free imidazole group. The tyrosine residues have a pK value of approx. 10, but their average reactivities are substantially less than for a free phenolic group. At alkaline pH values above 8 the reactivity of all the functional groups show sharp discontinuities, indicating that insulin is undergoing a structural change that alters the properties of these groups.

Acetic Anhydrides↗

Behavioral deficit in phenylketonuric rats: role of aromatic acid metabolites of phenylalanine.

To investigate the relationship between the biochemical and behavioral deficits in phenylketonuria (PKU), we treated rats from Postnatal Days 2 through 21 with p-chlorophenylalanine plus L-phenylalanine to simulate PKU or with one of the following aromatic acid metabolites of phenylalanine phenylacetate, phenylpyruvate, phenyllactate, and mandelate. Behavioral tests were begun at about 9 weeks of age. Differences between experimental and control animals were found only in the water maze and in the open field. In the former, PKU rats required significantly more trials to reach criterion than controls. None of the single metabolite-treated groups exhibited a similar learning deficit. In the open field, PKU and mandelate-treated rats were hypoactive compared with controls, whereas phenylacetate- and phenylpyruvate-treated rats wee hyperactive. These results demonstrate a lack of congruence between morphological and behavioral effects of treatment, suggesting that performance deficits in PKU rats may be due to interactive effects of 2 or more metabolites.

Age Factors↗

Effects of fostering on seizure activity in the Mongolian gerbil.

The purpose of this experiment was to ascertain whether seizure propensity in Mongolian gerbils is affected by differences in behavior and/or nurturing ability of seizure-prone (SP) and nonseizure-prone (NSP) parents. Day-old SP and NSP pups were cross-fostering, while other SP pups were fostered to SP parents. Matched nonfostered littermates served as controls. The SP gerbils fostered to NSP parents exhibited delayed onset of seizure activity whereas SP gerbils fostered to SP parents did not. Neither familial defect underlies seizure-proneness in gerbils, but that expression of this tendency is affected by parental behavior and/or nurturing ability.

Animals↗