PubMed Health⌕ Search

Biomedical subjects

D C Hoffman

Publications and source records attributed to D C Hoffman.

43 records · Page 3Linked to original sources
PubMed1970

Surgical treatment of severe attacks of ulcerative colitis, with special reference to the advantages of early operation.

The management and outcome of 258 severe attacks of ulcerative colitis from 1952 to 1969 has been reviewed. If remission did not occur during an initial course of intensive medical treatment, including administration of corticosteroids, operation (generally ileostomy with proctocolectomy or subtotal colectomy) was performed. This took place some 12 to 17 days after admission as a rule during the years 1952-63, but usually within five to seven days from 1964 to 1969.Roughly half the attacks underwent spontaneous remission during the two periods, but the medical mortality was 4.8% in the former and 0.7% in the latter, the operative mortality 20.0 and 7.0%, and the overall mortality 11.3 and 4.5% respectively. The lowering of the mortality was particularly striking in severe first attacks and in severe attacks in patients over 60 years of age.Perforation of the colon was found in 21 cases, or nearly 20% of 112 patients coming to operation during attacks, being commoner in the first period (32.5%) than in the second (11.1%). The immediate mortality of all such operations was 11.6%; in cases with perforation it was 28.6%.Acute colonic dilatation was observed in 28 cases. All but one were treated by emergency colectomy, at which the colon was noted to be perforated in 11. The mortality of these operations was 18.5%.Follow-up of the 140 patients who survived without coming to operation during their attacks shows that 52 (37.1%) subsequently underwent surgical treatment either during further attacks or electively.Though all 258 attacks were thought at the time to be due to ordinary ulcerative colitis, subsequent pathological examination of operative specimens derived from 98 patients who came to urgent or subsequent operation during the 1964-9 period revealed that the lesion in the large bowel was Crohn's disease in 17 instances.

Acute Disease↗
PubMedDate not supplied

The use of place conditioning in studying the neuropharmacology of drug reinforcement.

The place conditioning paradigm has proven successful in identifying the neural mechanisms of drug reinforcement. Two classes of drugs, opiates and psychomotor stimulants, have received the most study, and in each case an important role for DA neurons of the mesolimbic system has been established. Moreover, both receptor subtypes, D1 and D2, appear to be involved. Despite this progress, the substrates of drug reward are not completely understood. First, a role for DA has not been established for all stimulants: DA receptor blockade failed to affect conditioned place preferences produced by the stimulants methylphenidate, nomifensine, or bupropion. Second, preliminary evidence suggests that intact serotonergic transmission is important in morphine place conditioning, but a similar consistent finding has not been observed with amphetamine place conditioning. Further study may reveal an interesting dissociation of serotonin's role in the rewarding effects of psychomotor stimulants and opiates. Finally, the role of the opiate receptor subtype kappa is not known; also, the significance of the several anatomical sites that support opiate place conditioning remains unclear.

Animals↗
PubMedDate not supplied

Receptor subtype-specific dopaminergic agents and conditioned behavior.

Dopaminergic neurotransmission has been implicated in reward-related learning. With the advent of pharmacological agents that are relatively specific for D1 and D2 dopamine receptors, it has become possible to assess the role of these receptor subtypes in this form of learning. Antagonist studies have shown that either D1 or D2 receptor blockers produced extinction-like effects on operant responding for food, water or brain stimulation reward and in drug self-administration paradigms. They also blocked place preference learning based on amphetamine. Agonist studies showed that D2, but not D1 agonists were self-administered, produced place preferences and enhanced responding for conditioned reward. It may be that the dopaminergic signal at the D1 receptor is important for the establishment and maintenance of reward-related learning. From this point of view the effects of D1 antagonists can be understood. D2 antagonists may produce extinction-like effects because they lead to increased dopamine release and, therefore, indirectly mask the dopamine signal at the D1 receptor. D1 agonists may fail to produce reward effects because they, unlike D2 agonists, directly mask the dopaminergic signal at the D1 receptor.

Animals↗
PubMedDate not supplied

Receptor subtype-specific dopaminergic agents and unconditioned behavior.

When all of the data concerning the role of D1 and D2 receptors in the control of unconditioned behaviors are taken together a fairly consistent picture begins to emerge. Considering first the normosensitive animals, it appears that D1 and D2 receptors are interdependent in their involvement in the control of locomotor activity. Stimulation of either receptor subtype leads to increases in activity although D2 agonists generally have a larger effect on activity than D1 agonists. Subeffective doses of D1 and D2 agonists (or D1 and D2 antagonists) have a synergistic action when co-administered. Injections of antagonists specific for either receptor subtype leads to a decrease in unstimulated locomotor activity or a diminution in the effects of agonists stimulating either receptor subtype. Besides locomotor activity, stimulation of D2 receptors produces yawning but a consistent effect on grooming has not been seen; D2 receptor stimulation also produces stereotyped behaviors. Again, there seems to be an interdependence between the two receptor subtypes; yawning or stereotypy produced by D2 receptor stimulation is blocked by either D2 or D1 antagonists. Stimulation of D1 receptors produces grooming and small perioral movements but not stereotyped behaviors like those typically seen following large doses of D2 agonists or DA agonists not specific a receptor subtype. Unlike D1 receptor-stimulated locomotor activity which is antagonized by D2 receptor blockers, grooming and perioral movements are not (but see Ref. 81). Thus, D1 receptor-mediated grooming and perioral movements seem to be exceptions to the otherwise general finding that co-stimulation of the two receptor subtypes needed for the expression of D1 or D2 agonist effects in normosensitive rats and mice. The apparent need to stimulate both D1 and D2 receptors to produce locomotor and some other unconditioned behaviors in normosensitive animals is lost in chronically denervated animals that are supersensitive to the effects of DA or DA agonists. However, there appear to be important species differences. Generally, in rodents undergoing unilateral or bilateral 6-OHDA-induced destruction of the nigrostriatal DA system, the locomotor effects of D1 agonists are not blocked by D2 antagonists and those of D2 agonists are not blocked by D1 antagonists. Similar results have been reported following chronic treatments with catecholamine depleting drugs. Thus, stimulation of either D1 or D2 receptors alone in DA supersensitive rodents appears to be sufficient to produce locomotor activity. In primates made DA supersensitive either with MPTP or as a result of Parkinson's disease, on the other hand, D2 but not D1 agonists are effective in reversing locomotor deficits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗