Endothelial covering of biological artificial heart valves.
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Biomedical subjects
Publications and source records attributed to D Hoffman.
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Intraoperative massive pulmonary embolism is extremely rare. We describe such a case in a patient treated for a prolonged period preoperatively with intravenous heparin after an acute myocardial infarction and unsuccessful attempt at angioplasty, emphasizing that the problem should be borne in mind to facilitate expeditious and appropriate management. A clue to the diagnosis is interruption of venous return that is not due to a kink in the cannulae.
BACKGROUND: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification in the absence of aldehyde. METHODS AND RESULTS: Bovine pericardium was 1) treated with 0.625% glutaraldehyde and stored in 4% formaldehyde, 2) treated with 99.5% glycerol, and 3) treated with 99.5% glycerol and stored in formaldehyde (0.25-4%). The treated pericardium was used to construct stentless mitral valve prostheses (of a single pattern) that were implanted in weanling sheep. After the animals were killed, a strip of anterior cusp from annulus to papillary muscle was processed and examined by scanning electron microscopy for the presence of host endothelial growth. Avoidance of aldehyde allowed host endothelial growth in all cases (six of six), and pure aldehyde treatment inhibited growth in five of six animals. Exposure to aldehyde after glycerol treatment interfered with endothelialization significantly; after longer periods of implantation, however, endothelial growth occurred almost invariably in this group (12 of 13 implanted longer than 200 days). For this group, there was a statistically significant difference for duration of implantation between the valves that grew endothelium and those that did not (218.4 +/- 61.9 versus 128.5 +/- 65.4 days). CONCLUSIONS: Aldehyde treatment inhibits endothelial growth. With glycerol treatment, growth is uniformly present. Limited exposure to aldehydes after glycerol treatment inhibits endothelial growth, but this effect was ameliorated by prolonged implantation. The possibility of host endothelium-covered, noncalcifying bioprostheses is now real.
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The tumor initiating activity on mouse skin of benzo[a]pyrene (BaP), 7,10-dimethylBaP, and 10-methylBaP was determined. Each compound was tested at initiating doses of 50 microgram and 100 microgram with promotion by application 3 times weekly of 2.5 microgram tetradecanoylphorbol acetate. BaP induced tumors in 40% (100 microgram) and 25% (50 microgram) of the animals. No tumors were observed in either group treated with 7,10-dimethylBaP. In the groups treated with 10-methyl-Bap, the incidence of tumor bearing animals was 20% at both doses. These results and the results of previous studies on other methylated BaP derivatives suggest that the mechanism of activation of these compounds is similar to that observed for the parent hydrocarbon and probably involves formation of an angular ring diol-epoxide or epoxide.
1. Rhesus monkeys were trained to exert steady biting forces of 3--60 N for 1--2 sec. This behaviour was well maintained while sinusoidal or step opening and closing movements were imposed on the jaw. 2. The amplitude of the force modulation during sinusoidal stretching was divided by the amplitude of movement to obtain the magnitude of stiffness. This estimate was made at frequencies from 2 to 50 Hz at amplitudes of 100 and 500 micrometer (half the peak-to-peak movement at the incisors). 3. Peak magnitudes of stiffness were seen with frequencies of 8--15 Hz when the amplitude of movement was small; there was a great deal of variation between individual animals. This variation was most striking with mean forces of 25--35 N. The stiffness was greatest in animals that showed considerable spontaneous tremor, and the highest levels of stiffness were often recorded with frequencies near which tremor amplitude was large. A marked phase lag in the force response was often seen during small amplitude stretching at 8--30 Hz. 4. Estimates of stiffness for larger amplitude (500 micrometer) stretching showed less variation; the magnitude of stiffness showed maximum values below 10 Hz and a minimum at 15--30 Hz. Force always showed a phase lead on position although this lead became small in the frequency range where with smaller movement there had been phase lags. The magnitude of stiffness increased with increasing mean force. 5. Bilateral electrolytic lesions were made in the brain stems of three animals; they reduced by over 95% the expected number of cells in the mesencephalic nucleus of the fifth cranial nerve on either side. These lesions interrupted the afferent pathway for the stretch reflex and so abolished excitatory electromyogram (e.m.g.) responses to step stretches of the jaw closing muscles. 6. Such reflex responses as persisted after the lesions were small and inhibitory. E.m.g. silences followed both step stretch and release; the response to release was a 'load compensation' that could not be attributed to spindle afferents. 7. After the lesions the responses to movements of 100 micrometer showed neither negative values for the phase nor marked peaks in the stiffness magnitude at low frequencies; these features therefore take origin in the action of the stretch reflex. The stiffness that was measured after the lesions may be attributed to the non-reflex components resisting stretch, particularly to the properties of the contracting muscles. Thus, the phase of the force response was markedly advanced at all frequencies and the stiffness seen for 100 micrometer was similar to that for 500 micrometer. Stiffness increased with increasing mean force, as before surgery. 8. Vector subtraction of the stiffness seen at each frequency after interrupting the stretch reflex from that seen before doing so gave a quantitative estimate of the strength of the stretch reflex. The reflex activity calculated in this way showed attenuation and progressive phase lag as the frequency increased above 10 Hz...
Epidemiological studies have implicated three factors in the overall increase of lung cancer--tobacco, especially cigarette smoking, urban pollution and, to a lesser extent, certain industrial respiratory environments. Some data were discussed on carcinogenic industrial inhalants, and on the possible effect of urban pollution. The reduction of pollution and that of specific environmental agents is stressed. Laboratory studies on the identification of carcinogens in cigarette smoke and their reduction toward the "less harmful cigarette" represent a part of this aspect.
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A series of 6,11-dihydrodibenz[b,e]oxepin-2-acetic acids has been evaluated for both antiinflammatory and analgetic activity in the carrageenan paw edema and phenylquinone writhing assays. The requirements for optimal activity in this series appear rather specific: (a) an unsubstituted 6,11-dihydrodibenz[b,e]oxepin nucleus and (b) a carbonyl group in the 11 position. One derivative, 6,11-dihydro-11-oxodibenz[b,e]oxepin-2-acetic acid (11), has been selected for further study.
HP 549 is an orally effective non-steroidal anti-inflammatory agent with moderate analgesic and antipyretic activity. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. HP 549 also inhibits carrageenan-induced paw edema in the rat, an activity which is not altered by adrenalectomy. The analgesic activity of HP 549 was demonstrated in phenylquinone writhing. However, HP 549 produced variable results in the Randall-Selitto analgesia test. The anti-pyretic activity of HP 549 appears to be weak. HP 549, unlike other pharmacologically active anti-inflammatory drugs, does not produce gastric irritation at effective doses and is 45 times less ulcerogenic than indomethacin. Also the acute therapeutic indices for HP 549 are more favorable than for indomethacin.
Synthesis of 1'-methyl-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (7a, HP 365) and the demethyl analogue 9a (HP 505) was prompted by recognition of an aminoalkyl(aryl)isobenzofuran moiety common to the antidepressants talopram (Lu 3-010) and trans-10,11-dihydro-5,10-epoxy-5-[3-(methylamino)propyl]-5H-dibenzo[a,d]cyclohepten-11-ol (MK-940). Convenient laboratory synthesis of 7a was provided by lithiation of 2-bromobenzhydryl methyl ether, followed by addition of 1-methyl-4-piperidone and acid-catalyzed cyclization. N-Dealkylation by standard methods afforded 9a. Synthesis of analogues was stimulated by discovery of marked inhibition of tetrabenazine-induced ptosis for lead compounds 7a and 9a. Optimal antitetrabenazine activity is associated with the 3-phenylspiro-[isobenzofuran-1(3H),4'-piperidine] moiety where nitrogen is basic. Modification of this moiety by introduction of large nitrogen substituents or a C-3 substituent greater than H significantly reduced antitetrabenazine activity. A series of analogues with aromatic substituents was investigated; however, few of these compounds were significantly more active than 7a and 9a. Compound 9a was selected for additional studies.
3H-corticoids were localized by autoradiography in small neurons in the area of the magnocellular paraventricular nucleus of mallard ducks. Correlative data show that: (1) the label is principally unmetabolized steroid, (2) the hypothalamus competitively binds corticosterone, (3) the paraventricular nucleus contains immunoreactive neurophysin, is richly innervated by boutons of monoaminergic nerves and is involved in the adaptive response to osmotic stress.
Multiple doses of oxytetracycline were administered at regular but different intervals to groups of patients undergoin orthopaedic surgery. It was found that doses of the drug were incorporated at bone growth sites most frequently if the intervals between those doses were 3 or 6 days. This suggests a biorhythm in human bone growth with a periodicity of 3 days: this biorhythm may be altered by hormones or drugs.