Combined administration of agonist-antagonist as a method of regulating receptor activation.
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Biomedical subjects
Publications and source records attributed to R M Stein.
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Continuing medical education plays an essential role in efforts to improve physician performance. This article deals with remedial or personalized physician education. The experience of selected institutions and state organizations that have and/or continue to provide such remedial education is reviewed. The emphasis of remedial or focused physician education is educational enhancement, not suspension or revocation of license.
OBJECTIVE: To evaluate concurrent administration of mecamylamine (nicotine antagonist) with nicotine skin patch treatment for smoking cessation. METHODS: This was a randomized, double-blind, placebo-controlled trial. Forty-eight healthy smokers who smoked at least one pack per day were studied at an outpatient smoking cessation research clinic. The subjects ranged in age from 20 to 40 years. Intervention with the nicotine skin patch (6 to 8 weeks) plus oral mecamylamine (2.5 to 5 mg twice a day for 5 weeks) was compared to nicotine patch plus placebo. Mecamylamine treatment began 2 weeks before smoking cessation. The primary outcome was continuous abstinence through 7 weeks after cessation (1 week after treatment), confirmed by expired air carbon monoxide measurements. Secondary measures included point abstinence at 7 weeks, continuous abstinence at 6- and 12-month follow-up, and self-reported withdrawal symptoms. RESULTS: The continuous abstinence rate at 7 weeks was three times higher in the mecamylamine condition: 50% versus 16.7%, p = 0.015. Point abstinence at 7 weeks was 58% for mecamylamine versus 29% for placebo, p = 0.044. At follow-up, continuous abstinence remained higher for mecamylamine: 37.5% versus 12.5% at 6 months (p = 0.046) and 37.5% versus 4.2% at 12 months (p = 0.004). Mecamylamine also significantly reduced craving for cigarettes, negative affect, and appetite. CONCLUSIONS: Agonist-antagonist therapy, consisting of the nicotine patch with oral mecamylamine, may substantially improve current smoking cessation treatment.
We studied the histotoxic effects of mitomycin C and 5-fluorouracil (5-FU) in the eyes of New Zealand white rabbits using light microscopy. Twenty-four eyes of 24 rabbits received subconjunctival injections of mitomycin C (0.025, 0.05, 0.10, 0.20, 0.40 or 0.80 mg/mL) or 5-FU (10.0 mg/mL), either alone (0.25 mL) or in combination with anterior chamber injections (0.05 mL), once daily for 4 consecutive days. Two eyes of two rabbits received subconjunctival and anterior chamber injections of unpreserved sterile saline. The eyes were examined regularly for external signs of toxicity and were enucleated 4 weeks after the last injection. Mitomycin C produced considerable tissue damage in the anterior segment, the severity being related to both the concentration and the route of administration. Eyes that received both subconjunctival and anterior chamber injections showed more damage than those that received subconjunctival injections alone. At the highest concentration of mitomycin C the cornea was inflamed, with stromal necrosis and marked endothelial loss. Hemorrhagic iris necrosis was also seen. In contrast, the 5-FU-treated eyes showed no microscopic evidence of toxicity. We conclude that there is greater risk of toxic anterior segment effects when mitomycin C is used as adjunctive therapy following filtration or pterygium surgery.
A variety of studies have shown that nicotine skin patches are effective in promoting smoking cessation. This study replicated this effect, in addition, nicotine skin patches were found to decrease a variety of withdrawal effects, including craving for cigarettes, negative affect, hypoarousal, and increased appetite. This study also assessed the depressive symptoms shown by smokers before and after they quit smoking. Control subjects showed a significant increase in depressive symptoms after smoking cessation, whereas the subjects given the nicotine skin patch were not as affected. If the subjects slipped and smoked a cigarette during the time they were wearing the patch, they were asked to rate the effects of that cigarette. These "slip" cigarettes were rated significantly lower in satisfaction and good taste by subjects in the nicotine patch group than by controls. The nicotine skin patch may improve smoking cessation rates both by reducing nicotine withdrawal effects and by reducing the reward of slips back to smoking. This latter effect may prove to be effective in preventing slips from turning into relapses.
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OBJECTIVE: This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD). METHOD: Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale. RESULTS: Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD. CONCLUSIONS: The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.
BACKGROUND: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. METHODS: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. RESULTS: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). CONCLUSION: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed.
The keratometer and photokeratoscope have long been the standard instruments for measuring corneal curvature. The recent development of computer-assisted photokeratoscopy has greatly enhanced the evaluation of corneal topography, helping improve our understanding of both normal and abnormal topography and their influence on visual acuity. The authors review normal corneal topography and compare various tools, both new and old, currently available for evaluating corneal contour. Case studies are presented to illustrate some of the clinical and research applications of computer-assisted photokeratoscopy in an ophthalmology practice. Future applications of computer-assisted photokeratoscopy include intraoperative topography, the design of custom-fitted contact lenses and combination with ray-tracing analysis.
Two cases of bilateral malignant glaucoma are presented. In one case the condition developed sequentially in the two eyes; pars plana vitrectomy was eventually needed in the operated eye, whereas the condition responded to medical treatment in the fellow eye. In the second case the two eyes were involved simultaneously nearly 1 year after surgery, and the glaucoma responded to medical treatment.
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Cytomegalovirus (CMV) infection in patients with the acquired immunodeficiency syndrome (AIDS) can present as either disseminated disease, pneumonitis, retinitis, gastroenteritis, neuropathy, or a subclinical infection. We report a patient whose initial manifestation of CMV infection was severe central airways obstruction due to necrotizing tracheitis. At bronchoscopy, the lesion appeared deeply ulcerated, distinctly different from previously described airway lesions in patients with AIDS. Mucosal biopsies showed characteristic intranuclear and intracytoplasmic inclusions and cultures yielded only CMV. The patient responded partially to ganciclovir, steroids, and antibiotics against suspected anaerobic superinfection but died as a result of central nervous system disease believed due to toxoplasmosis or lymphoma. CMV infection of the upper airway should be considered in the patient with AIDS presenting with atypical cough or stridor and ulcerated endobronchial lesions.
A rare lymphoepithelial lesion of the pancreas was discovered incidentally at autopsy. This lesion is composed of epithelial-lined cystic spaces encompassed by lymphoid stroma, similar to lesions reported in the salivary glands. Review of the literature revealed only three similar cases. This lesion should be considered in the differential diagnosis of pancreatic cysts.
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We examined 50 patients to determine whether differences exist between the initial clinical signs and symptoms associated with infected vs sterile corneal infiltrates. A detailed history regarding contact lens use and ocular symptoms was taken, after which a careful slit-lamp examination was performed. The ocular findings were correlated with the results of corneal cultures. Increased pain (P less than .001), discharge (P less than .0001), epithelial staining (P less than .0001), and anterior chamber reaction (P less than .0001) were associated with infected ulcers. Sterile infiltrates were usually smaller; multiple or arcuate; and without significant pain, epithelial staining, or anterior chamber reaction.
Management of the intraocular lens (IOL) at the time of penetrating keratoplasty (PK) for pseudophakic bullous keratopathy has been based on lens-related factors and coexisting anterior segment abnormalities. The authors reviewed the results of PK for 102 cases of pseudophakic bullous keratopathy (43 anterior chamber, 50 iris-supported, and 9 posterior chamber) with respect to: (1) the type of IOL, (2) coexisting abnormalities, and (3) management of the IOL at surgery. Graft failure after 2 years of follow-up was: (1) retained iris-supported IOLs, 9%; (2) retained anterior chamber IOLs, 60%; (3) retained posterior chamber intraocular lenses (PC IOL), 0%; (4) removed IOLs, 9%; and (5) exchanged IOLs, 20%. After 5 years of follow-up, 13 of 13 PKs with retained closed-loop anterior chamber IOLs had failed. Visual results were best in eyes with retained iris-supported, rigid anterior chamber or PC IOLs and when the IOL was removed without replacement. The authors recommend that closed-loop anterior chamber lenses and unstable lenses of any type be removed or exchanged and that well-fixated PC IOLs and iris-clip IOLs be retained at the time of PK for pseudophakic bullous keratopathy.