Nicotine-induced airway smooth muscle contraction: neural mechanisms involving the airway epithelium. Functional and histologic studies in vitro.

To assess the mechanism of and the role of the epithelium in nicotine-induced bronchoconstriction in vitro, we performed a combined functional and histologic study. Functional study: We suspended tracheal strips or rings from 16 ferrets (1124 +/- 561 g, mean +/- SD) in organ baths. Alternate tracheal strips had their epithelium removed. Dose-response curves to acetylcholine (ACh) and nicotine were established for pairs of tissues with and without epithelium, each pair receiving only one dose of nicotine. Nicotine induced brief muscle contractions not exceeding 25% of the ACh-induced maximum. Contractions were blocked by hexamethonium and 10(-7) M atropine and were abolished or inhibited strongly by tetrodotoxin (TTX), suggesting the involvement of nicotinic neuronal and muscarinic smooth muscle receptors. Removal of the epithelium strongly inhibited contractions at concentrations of nicotine greater than 3 x 10(-5) M which completely removed any dose-response effect. ACh-induced contractions were unchanged, demonstrating smooth muscle integrity. We suggest that the removal of the epithelium attenuates nicotine-induced bronchoconstriction through the removal of nerves running in or close to the epithelium. Histologic study: In tracheae from 15 ferrets (8 male, 7 female), mean weight (+/- SD) 1288 (+/- 470) g, we examined 4 techniques of epithelium removal: (1) gentle scraping with a scalpel blade moved backwards (away from the cutting edge), (2) moving a Q-tip through the unopened tracheal tube without lateral pressure, and (3, 4) stroking the mucosa of opened tracheal segments with a Q-tip, exerting (3) light or (4) moderate pressure. All methods were equally (97%-100%) efficient in removing the epithelium but differed in the amount of damage caused to the basement membrane and/or submucosal tissue. Method (2) caused less damage to the basement membrane than the other methods but still removed almost one-third of it. The study showed that complete removal of the epithelium is at the expense of the submucosa and that a given result of "epithelium removal" is also attributable to removal of the neighboring subepithelial structures.

[Stimulation of mucous glands of the respiratory tract by neuropeptides: comparison of exogenous administration and endogenous liberation]. / Stimulierung von Schleimdrüsen der Atemwege durch Neuropeptide: Vergleich exogener Zufuhr und endogener Freisetzung.

Exogenous substance P is a powerful stimulant of tracheal gland secretion but the contribution of endogenous neuropeptides to neurogenic gland secretion is unknown. Using the Ussing chamber technique, we measured the secretion of radiolabeled macromolecules from submucosal glands in the ferret. Neurokinins caused gland secretion through a neurokinin-1 (NK-1) receptor. Gland secretion caused by electric field stimulation of postganglionic nerve endings was not inhibited by a substance P antagonist and was not augmented by agents known to prevent neurokinin degradation in the tissue. We conclude that the release of endogenous neurokinins plays no rôle in neurally evoked gland secretion. This is despite the fact that endogenous neurokinins have been shown to be involved in vagally induced airway smooth muscle contraction and increased capillary permeability in the same species.

Retention of serrated endodontic posts with a composite luting agent: effect of cement thickness.

When Prosthodent composite was used as a cementation material for endodontic posts (ParaPost), adaptation of the post to the canal was not crucial. Changes of the composite layer thickness up to 500 microns did not decrease retention. Variation in the diameter of the posts did not effect the retention. The retention obtained for the combinations of posts and cements was high and suitable to resist dislodgment of the posts. Consequently, the thinnest post in the root canal, cemented with a composite is recommended. Thus the removal of tooth structure is unnecessary because the cylindrical preparation is formed in the composite.

Abnormalities of the cardiovascular response to cold pressor test in type 1 diabetes. Correlation with blood glucose control.

Left-ventricular (LV) function in type 1 diabetics without clinical heart disease was compared with that found in matched normal subjects. Although diabetics had a normal LV ejection fraction (66% +/- 6%), they showed a trend toward smaller left ventricles. Their cardiovascular response to a cold pressor test was abnormal and cardiac function after the cold pressor test correlated with hemoglobin A1c levels: Average hemoglobin A1c was inversely related to ejection fraction and early filling volume and directly related to the ratio of pre-ejection period to ejection time (PEP/LVET) after a cold pressor test. Hemoglobin A1c at the time of study correlated more closely with PEP/LVET after cold pressor test than did the six-month average hemoglobin A1c level, suggesting that cardiac function fluctuates with recent changes in blood glucose control. Thus, even when diabetics have a normal LV ejection fraction, an abnormal cardiovascular response to stress may still be present, and such abnormalities correlate with blood glucose control.

Oral contraceptives abolish luteal phase exacerbation of hyperglycemia in type I diabetes.

PIP: For some time it has been recognized that postovulatory exacerbation of hyperglycemia contributes to the instability of diabetes in many women of reproductive age. It has been suggested that increasing plasma levels of progesterone and estrogen may induce insulin resistance and consequently lead to increased hyperglycemia during the luteal phase of the menstrual cycle. Due to the fact that menstrual cycles in a given woman may vary in length and that it takes patients several days on intermediate or long-acting insulin to achieve a steady state with regard to any dosage adjustment, it is difficult to design an insulin regimen that maintains euglycemia throughout the menstrual cycle in these labile patients. Recognition of this problem led to trying a nonsequential low estrogen contraceptive as adjunctive therapy in a 20-year old woman with insulin dependent diabetes mellitus. The patient consistently suffered an exacerbation of hyperglycemia after ovulation in each cycle, lasting until the onset of menses. On 1 occasion the patient developed frank diabetic ketoacidosis. For the first 2 cycles on Lo Ovral, the hyperglycemia was postponed from the 1st postovulatory day until day 18-19 of the cycle. It was reasoned that the serum estrogen and/or progestin level might be building cumulatively, and the oral contraceptives (OCs) were subsequently withdrawn at day 19 of the cycle rather than day 21. A maximum blood glucose level of 400 mg/dl was attained at day 19 and was treated with additional regular insulin. Levels in excess of 240 mg/dl did not recur during that cycle. The following cycle OC therapy was interrupted at day 18; no blood glucose level in excess of 240 mg/dl occurred that month. Hemoglobin A1c fell from a pre-OC treatment value of 12.4% to the current A1c of 9.7%. A modest increase in blood pressure has occurred, but this is easily managed with a 2 g sodium diet and 25 mg of hydrochlorothiazide daily. On the basis of this experience, a controlled trial is warranted of low dose estrogen nonsequential OCs in lean, nonsmoking, 18-30 year old women with insulin dependent diabetes mellitus with postovulatory hyperglycemia.^ieng

Impact of peer review in reduction of permanent pacemaker implantations.

Because of a sharp increase in the number of permanent pacemakers inserted at The Brooklyn Hospital between 1972 and 1976, a peer-review committee was established to monitor subsequent pacemaker implantation. Total initial implants declined from 48 to 22 per year in the two years that followed. The number of implantations for sinoatrial bradycardias declined from 50 to 27 and the number of implantations for intraventricular conduction defects declined from 32 to five in the two years after peer review, compared with the two years before. There was no change in the number of pacemakers implanted for complete or advanced heart block. Almost 10% of patients who received a pacemaker between 1972 and 1976 had other conditions that might have accounted for the events that precipitated the decision to implant a pacemaker. The symptoms for which the pacemaker was implanted persisted in 19% of patients, despite a normally functioning pacemaker system. Patients receiving a permanent pacemaker before peer review had a 17% one-year and a 43% three-year mortality. When a more critical patient selection process was instituted, a smaller percentage remained symptomatic (9% vs 19%) and three-year survival rate was improved (86% vs 57%). From 1977 through 1978, when permanent pacemaker implantations declined, the number of hospital, medical service, and coronary care unit admissions increased. It is concluded that peer review can have substantial impact on permanent pacemaker implantations.

Effect of blood glucose control on retinal vascular permeability in insulin-dependent diabetes mellitus.

Thirteen patients were instructed in a technique of self-management of insulin-dependent diabetes mellitus, using multiple home-monitored blood glucose determinations and multiple injections of regular insulin in conjunction with once-daily Ultra Lente insulin. Hemoglobin A1c and quantitative fluorescein fluorophotometry were used to assess blood glucose control and retinal permeability, respectively. In those patients achieving normal blood glucose control, retinal vascular leakage was statistically identical to that of a nondiabetic control population. In those patients less well controlled, retinal permeability did not differ statistically from values observed in a population of insulin-dependent diabetic patients under "standard" control. It is concluded that with "tight" control of blood sugar and normalized A1c hemoglobin, retinal permeability similarly is normalized.

Administration of aspartame in non-insulin-dependent diabetics.

A study was designed to determine the effect of the consumption of the nutritive sweetener aspartame on non-insulin-dependent diabetics. Forty-three adult diabetics between the ages of 21 and 70 completed a 90-day study; all were diabetics whose conditions were managed by diet and/or hypoglycemic agents. Participants in the blind study were instructed to continue their usual diet and to take two capsules of an assigned preparation three times daily with meals, either the aspartame or the placebo. The 1.8 g of aspartame administered is approximately three times the expected daily consumption of aspartame if used as a sweetener to replace sugar. Throughout the study subjects were examined for (1) symptoms of intolerance, (2) fasting plasma phenylalanine levels exceeding 4 mg/100 ml, and (3) deterioration of diabetic control. At the conclusion of the study subjects exhibited no symptoms that could be traced to the administration of aspartame or the placebo, and diabetic control was unaffected by the chronic administration of these substances. Aspartame seems to be well tolerated by non-insulin-dependent diabetics.

Glycerol-like contamination of commercial blood sampling tubes.

Commercial blood sampling tubes have been found to be heavily contaminated with a glycerol-like substance. Thus, use of these tubes may lead to falsely elevated plasma concentrations of glycerol.