Tobacco dependence: psychology, biology, and treatment strategies.
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Biomedical subjects
Publications and source records attributed to R W Johnson.
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Striking relationships were observed, in vitro, between the molecular constitution of synthetic entities, their aggregation-inhibitory potency (as determined in ADP-induced human blood platelet aggregation), and their cellular toxicity (as assessed by their inhibition of cultured mouse fibroblast L-cell growth). Effects exerted on platelets tended to reflect interactions between the molecules' aggregation-inhibitory specific functions and the platelets' corresponding target sites, while fibroblasts were generally more susceptible to the molecular constitution's hydrophobic character. The hyperbolic relationships between concentrations effecting 50% inhibition and slopes of concentration-response curves reflect net activity from both specific and nonspecific receptor site interactions, with the latter being dominant, and indicated that the assays approximated equilibrium systems. Plotting logarithm values of concentrations effecting 50% inhibition against logarithms of reciprocal slopes for concentration response curves yielded multiple regression coefficients of R = 0.97 (platelet aggregation-inhibitory potency) and R = 0.98 (fibroblast growth-inhibitory potency).
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Mechanically prepared isolated islets of Langerhans were cryopreserved in liquid nitrogen for a period of 4 days. Intraportal autotransplantation studies were performed on two groups of six pigs rendered diabetic by total pancreatectomy (group 2) or by partial pancreatectomy combined with streptozotocin (group 4) and compared with two control groups (groups 1 and 3, respectively). The pigs were assessed for survival, weight gain, glycosuria, polyuria, systemic blood sugar and insulin, and, in selected pigs, intravenous glucose tolerance tests. Results showed that partial pancreatectomy with streptozotocin was the better tolerated experimental diabetes. Variable control of hyperglycemia was obtained over an experimental period of 3 months. Random blood glucose returned to normal in one of six pigs in the totally pancreatectomized group and three of six pigs in the partial pancreatectomy and streptozotocin group. Despite these normal circulating glucose levels, imperfect glucose homeostasis was achieved as shown by the response to glucose tolerance testing. These results report blood glucose control after cryopreserved islet autotransplants in diabetic pigs but further study is still necessary to achieve consistency.
The patient who wishes to discontinue chronic hemodialysis poses a complex dilemma that crosses both ethical and psychiatric boundaries, but clearly demonstrates the role of the liaison psychiatrist in clarifying issues of diagnosis and informed consent. This paper presents an edited transcript of a clinical case conference where a 72-year-old man reviews his reasons for demanding that hemodialysis be discontinued. Issues of differential diagnosis and the question of autonomy and free will are discussed in the context of the tasks for the liaison psychiatrist.
One of the most powerful influences on cadaveric renal graft survival is the enhancing effect of blood transfusions from unrelated individuals (1, 2). However, the optimum number of transfusions required to achieve this effect remains controversial. Enhanced graft survival following only one or two transfusions has been observed (3), although graft survival has also been found to be better for multitransfused recipients (4). Extrapolating from their studies on mice, Wood et al. (5) suggested that only a very small volume of blood may induce the transfusion effect in humans. As the number of transfusions increases so does the risk of sensitizing the patient to produce lymphocytotoxic antibodies that may impair the chances of the patient receiving a crossmatch-negative kidney graft (6, 7). Thus the problem is to minimize the chance of sensitization while still maintaining the beneficial effect of blood transfusion.
Smoking has been viewed in divergent ways throughout history. While for some cultures it has been considered a crime, for others it has been invested with magical powers and even medicinal potential. In our century, society has come to realize the health risks associated with smoking. This has led to controversies between government and the tobacco industry as well as between physician and patient. In spite of their knowledge of its deadly consequences, many individuals are unable to stop smoking. The tenacity of this habit can be explained in terms of the various psychological motivations for smoking in combination with the physiologic addiction to nicotine. While some people are able to stop the habit, many relapse in spite of a variety of quitting methods. These range from the doctor's advice to stop, education programs, group and individual psychotherapies, behavioral techniques, hypnosis, and the use of nicotine gum. With a growing understanding of what distinguishes categories of smokers and with a new appreciation for the role of nicotine in addiction to smoking, more effective antismoking strategies can be fashioned to meet the specific needs of the potential quitter.
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In two consecutive prospective randomised trials cyclosporin A has been compared with conventional immunosuppressive therapy (azathioprine and steroids) and with cyclosporin combined with steroids. The present report is a 4 year review and includes 165 patients.Cyclosporin A alone had a significant advantage over conventional therapy at both 1 and 3 years (p = 0.02) for both patient and graft survival. No significant difference was seen when cyclosporin was combined with steroids. Nephrotoxicity was the most troublesome side-effect of cyclosporin A - but this resolved spontaneously on withdrawal of the drug.
Gradually altered synthetic entities were employed as molecular probes, and arachidonic acid, ADP, human alpha-thrombin and the Ca2+ ionophore A23187 as aggregation-inducing agents, in a comprehensive study on the response profile of human blood platelets with an emphasis on the effects of exogenous and increased intracellular Ca2+. Corroborating further previous conclusions, some representative carbamoylpiperidine derivatives, at concentrations effecting substantial inhibition of ADP-induced aggregation, failed to retain that effect when 5.0 mM Ca2+ was introduced into the otherwise identical test medium; reference compounds chlorpromazine and propranolol registered corresponding inhibitory patterns. At increased concentrations the compounds' inhibitory potency was regenerated even in the presence of 5 mM Ca2+. In fact, in sufficiently high concentrations, the compounds were even capable of inhibiting aggregation elicited by 15 microM of the ionophore A23187; so did chlorpromazine and propranolol. Another set of congeners revealed the striking sensitivity of ionophore A23187-induced human blood platelet aggregation to the surface active potencies of inhibitor molecules. The loss in inhibitory potency was directly related to the lesser hydrophobic character of the molecule.
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Islets of Langerhans, prepared by a new mechanical process and avoiding enzymatic digestion were frozen to -196 degrees C. Two rates of freezing were compared, instantaneous directly into liquid nitrogen and slow freezing at 1 degree C min-1. Post-thaw survival was greater after slow freezing. Three concentrations of dimethyl sulfoxide (DMSO) were compared. The 10% v/v concentration was found to give greater success than 20 or 30%. Contaminating exocrine tissue was found not to survive the freezing process.
The safety and durability of elective reconstructive procedures of the abdominal aorta and its major branches are universally accepted; however, late complications continue to threaten limbs and lives of a minority of patients. The strategy of managing such revascularization failures has received inadequate attention. Between February 1971 and July 1981, 76 patients underwent 83 remedial, transabdominal revascularization procedures because of failed reconstructions. Group I consisted of 34 patients with occlusive complications (0% remedial operative mortality rate); group II, 21 patients with prosthetic sepsis including graft-enteric fistula (14% operative mortality); group III, 11 patients with aneurysmal degeneration (36% operative mortality); and group IV, 10 patients with visceral ischemia (0% operative mortality). The remedial operative mortality rate for the combined groups was 7.9%. Limb preservation was the rule in group I (91%); however, 29% of limbs at risk in group II ultimately required major amputation (15% early, 14% late). All patients in group II without an established graft-enteric fistula were saved; however, three of ten with active hemorrhage died of the sequelae of hypovolemic shock. Progressive arteriosclerotic morbidity and massive intraoperative bleeding accounted for the high mortality rate in group III. Favorable results were obtained in reoperation for recurrent visceral ischemia (renal ischemia in five, mesenteric ischemia in five). On the basis of this experience, an aggressive surgical approach seems justified. First, complete bifemoral revascularization performed at the time of original operation should reduce the need for reoperation. Second, elective, transabdominal remedial arterial surgery can be done with acceptable morbidity and mortality rates. Third, graft-enteric erosions and periprosthetic sepsis must be treated aggressively to avoid life-threatening sepsis and hemorrhage. Finally, anatomic revascularization can be performed successfully after a suitable period following removal of an infected retroperitoneal prosthesis.
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