A pilot study of plasma caffeine concentrations in a US sample of smoker and nonsmoker volunteers

Even though 85% of adults drink caffeinated beverages daily, very limited studies on plasma caffeine concentration in the US population have been published. Smoking induces cytochrome P450 1A2 (CYP1A2), which is the main enzyme involved in caffeine metabolism. The current naturalistic pilot study explores plasma caffeine concentrations in a US sample, and presents a mathematical model of the relationship between caffeine intake and plasma concentrations for smokers and nonsmokers. Caffeine intake and average plasma caffeine concentrations from morning (7:30-9:30 a.m.) and afternoon (2:00-4:00 p.m.) samples were studied in 69 volunteers (21 smokers and 48 nonsmokers). The mean caffeine intake obtained from caffeinated beverages was 3.02 mg/kg/day, which is similar to the intake in the US population. Almost all subjects in the present sample (99%; 95% confidence interval [CI]: 96-100) had detectable plasma caffeine concentrations. Smokers had significantly higher caffeine intake than nonsmokers. The ratio of concentration/dose of caffeine from caffeinated beverages was approximately four-fold higher in nonsmokers (1.33 kgxday/l) than in smokers (0.29 kgxday/l). According to the model, the median plasma caffeine concentration was two- to three-fold higher in nonsmokers for each level of caffeine intake. Our model improves our understanding of the interactions between caffeine and smoking. Additional studies are needed to replicate the model. This model may help epidemiologists to correct for the effects of smoking on caffeine intake and pharmacologists to screen for the activity of CYP1A2.     

Serious respiratory infections can increase clozapine levels and contribute to side effects: a case report

Clozapine is mainly metabolized by the cytochrome P450 1A2 (CYP1A2), which may be inhibited by serious respiratory infections. This case report supports that a serious respiratory infection may increase clozapine levels and contribute to side effects. Plasma clozapine and norclozapine levels were monitored 17 times during 1 year. The concentration-to-dose ratio (C/D), an index of metabolic activity, was obtained by dividing the sum of plasma clozapine and norclozapine concentration (total clozapine concentration) by clozapine dose. The coefficient of variation (CV) of the total clozapine concentrations was calculated at different doses to provide a measure of the noise associated with determining clozapine concentrations in clinical practice. During a respiratory infection, the patient was taking 600 mg/day of clozapine. Clozapine levels were 1245 ng/ml (norclozapine 472 ng/ml), reflecting a decrease in clozapine metabolism by approximately a factor of 2. The high clozapine levels were associated with side effects (myoclonus and increased sedation). The C/D during the infection was 2.9, while the rest of C/Ds ranged between 1.0 and 1.6. CVs before and after the infection, at different doses, were always lower than 20%. When the level during the infection was included to calculate the CV on 600 mg/day, the CV increased to 54%. The theophylline literature, a prior case report and this case all suggest that if a clozapine patient develops a severe respiratory infection with fever, the psychiatrist must pay particular attention to any signs suggestive of major clozapine toxicity associated to a decrease in clozapine metabolism. If any of these signs appear, the psychiatrist may need to consider cutting the clozapine dose in half until the patient has recovered from the infection.     

Three-wall decompression technique using transpalpebral and endonasal approach in patients with Graves' ophthalmopathy

PURPOSE: To evaluate the effects of the three-wall decompression technique using transpalpebral and endonasal approach in patients suffering from Graves' ophthalmopathy. METHODS: In this prospective study, we present a consecutive series of 15 subjects (17 eyes) who were submitted to orbital decompression by removing the inferior and lateral walls using transpalpebral incision combined with a transnasal endoscopic resection of the medial wall. The surgical technique involved the preservation of the bone structure between the lamina papyracea of the ethmoid and the maxillary orbital floor. MAIN RESULTS: The mean ocular recession based on Hertel measurements was 6.00 mm (range, 4-9 mm). None of the patients presented pre-operation diplopia, and one developed post-operation diplopia. Visual acuity was preserved in all cases. CONCLUSION: It is safe and efficient to perform three-wall decompression, combining transpalpebral and endoscopic transnasal approach, with preservation of the bone structure and the bone lateral to the infraorbital canal with fixation by two titanium plates on the lateral edge and removal of intraorbital fat, which results in significant proptosis reduction and minimal complications.     

Neuroendocrine carcinoma of the nasal fossa. An independent entity?

We present one case of a neuroendocrine carcinoma of nasal fossa and paranasal sinuses, of aggressive behavior, which has been controlled with chemo-radiotherapy after a double postsurgical recurrence. We do a literature revision emphasizing the anatomopathologic differentiation of these tumors with the olfactory neuroblastomas, and the therapeutic controversies in advanced stages.     

Minimally invasive treatment of the nasal inverted papilloma

BACKGROUND: The purpose of this work is to evaluate our results in the treatment of the nasal inverted papillomas with an endoscopic approach using a retrospective case series. METHODS: Between 1993 and 2000 we treated 27 patients with nasal inverted papillomas. All patients underwent endoscopic nasal surgery under general anesthesia. None of the inverted papillomas extended outside of the paranasal sinuses. All tissue samples underwent polymerase chain reaction and hybridization in situ to detect genetic sequences of the human papilloma virus and Epstein Barr virus. RESULTS: The study population consisted of 16 men and 11 women with a median age of 52 years (range, 22-77 years). Ten patients (37%) had undergone a previous nasal surgery. The median follow-up was 5 years (range, 2-8 years). None of the patients presented with bilateral nasal involvement or a synchronous carcinoma. Seven patients underwent an additional surgical approach (two endoscopic approaches via a Caldwel-Luc approach, four sublabial approaches via a Caldwel-Luc approach, and one external ethmoidectomy). There were no surgical complications. Two patients (7%) had recurrent papilloma 4 and 6 years after surgery and again underwent endoscopic resection. The amplification both by polymerase chain reaction and hybridization in situ for human papilloma virus and Epstein Barr virus were negative in the specimens from all patients. CONCLUSIONS: According to the literature and our own experience, we believe that the initial surgical management of primary and recurrent inverted papillomas limited to the nasal cavity and paranasal sinuses should be endoscopic sinus surgery.     

Microalbuminuria: is it a valid predictor of cardiovascular risk?

Microalbuminuria strongly predicts cardiovascular morbidity and mortality, clinical nephropathy, and progression of renal disease in high-risk populations. We recommend screening patients with type 2 diabetes, older patients with type 1 diabetes, and older patients with stage 2 hypertension or higher (ie, > or = 160/100 mm Hg).     

Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy

BACKGROUND: Kashin-Beck disease is an osteoarthropathy endemic in selenium- and iodine-deficient areas around Lhasa, Tibet. OBJECTIVE: We assessed the efficacy of selenium supplementation on disease progression. DESIGN: A double-blind, randomized controlled trial of selenium supplementation was carried out in 324 children aged 5-15 y who had Kashin-Beck disease. Two hundred eighty children received iodized oil before being randomly assigned to receive selenium or placebo, and a control group of 44 subjects was not supplemented at all. Clinical and radiologic signs, selenium status, urinary iodine, and thyroid function were evaluated at baseline and at 12 mo. RESULTS: The frequencies of joint pain, decreased joint mobility, and radiologic abnormalities were not significantly different between the 3 groups at 12 mo. Height-for-age z scores increased significantly in the subjects who received placebo and iodine or selenium and iodine. In contrast, unsupplemented control subjects did not recover from growth retardation. Serum selenium concentrations at 12 mo were within the reference range and were significantly greater in the selenium-iodine group than in the placebo-iodine group. Serum thyroid hormone concentrations were within the reference ranges after the administration of iodine, and these values were not significantly affected by selenium supplementation. CONCLUSIONS: The results of this study do not rule out the possibility that selenium may help to prevent the occurrence of Kashin-Beck disease. However, selenium supplementation had no effect on established Kashin-Beck disease, growth, or thyroid function once iodine deficiency was corrected. These results suggest that iodine, but not selenium, deficiency should be corrected in Tibetan children with Kashin-Beck disease.     

The efficacy of a local ascorbic acid-rich food in improving iron absorption from Mexican diets: a field study using stable isotopes

BACKGROUND: One potentially sustainable approach to improving iron status at the community level is to encourage the consumption of local ascorbic acid-rich foods, in conjunction with meals high in nonheme iron. OBJECTIVE: The study, conducted in rural Mexico, measured stable isotopes of iron to evaluate the effect on iron absorption of the addition of 25 mg ascorbic acid as agua de limón (limeade) to 2 typical meals per day for 2 wk. DESIGN: Fifteen nonpregnant, nonlactating, iron-deficient (ferritin < 12 microg/L) women (x +/- SD age: 28.3 +/- 7.7 y) fasted overnight and were brought to a community clinic. After an initial blood sample, subjects consumed 0.25 mg (57)Fe with both breakfast and lunch for 14 d. On day 29, another blood sample was taken, and a reference dose of 2.7 mg (58)Fe with 25 mg ascorbic acid was given. For the following 15 d, participants consumed 0.25 mg (57)Fe added to both breakfast and lunch with 25 mg ascorbic acid added to each meal as limeade. A final blood sample was taken on day 59. RESULTS: Iron absorption was calculated from recovery of isotopes in blood obtained 14 d after administration of each isotope. When 25 mg ascorbic acid as limeade was added to test meals twice a day for 2 wk, iron absorption increased significantly (P < 0.001) in every subject: the mean absorption rose from 6.6 +/- 3.0% to 22.9 +/- 12.6%. CONCLUSIONS: The consumption of 25 mg ascorbic acid as limeade twice daily with meals substantially improved iron absorption and may improve the iron status of nonpregnant, nonlactating, iron-deficient women.